RNA POLYMERASE TRANSCRIPTION FACTOR

Abstract: An RNA polymerase transcription factor has been isolated and characterized which increases the rate of transcription elongation by RNA polymerase II.

Description: RNA POLYMERASE TRANSCRIPTION FACTOR RELATED APPLICATION This application corresponds to United States application Serial No. 08/524,757 filed September 7, 1995 which is a continuation-in-part of copending application Serial No. PCT/US94/13621 filed November 29, 1994, which is a continuation-in-part of United States application Serial No. 08/160,087 filed November 30, 1993. TECHNICAL FIELD This invention relates to the field of RNA polymerase transcription factors. BACKGROUND OF THE INVENTION Transcription is the first stage in gene expression and the principal step at which it is controlled. It involves synthesis of an RNA chain representing the coding strand of a DNA duplex. Transcription takes place by the usual process of complementary base pairing catalyzed by the enzyme RNA polymerase. This reaction can be divided into three stages: initiation; elongation; and termination. In eucaryotic systems, RNA polymerase associates with several other enzymes and factors at a sequence of DNA which defines a promoter. Accurate initiation requires a number of initiation factors and is an important point at which transcription is controlled. Elongation describes the phase during which the RNA polymerase moves along the DNA and extends the growing RNA chain. As the RNA polymerase moves, it unwinds the DNA helix to expose a new segment of the template in single-stranded form. Nucleotides are covalently added to the 3' end of the growing RNA chain forming an RNA-DNA hybrid in the unwound region. Additionally, the RNA that was made previously is displaced from the DNA template strand, which pairs with its original partner to reform the duplex helix. Thus, elongation involves the disruption of DNA structure to form a transiently unwound region that exists as a hybrid RNA-DNA duplex and a displaced single strand of DNA. Termination involves recognition by the RNA polymerase of the point at which no further bases should be added to the chain, followed by dissociation of RNA polymerase from both the DNA template and the newly synthesized RNA chain. Messenger RNA synthesis is a complex biochemical process requiring the action of multiple transcription factors, including initiation and elongation factors, that control the activity of the RNA polymerase at both the initiation and elongation stages of transcription. Several of these factors are known to be essential for initiation and are referred to as factors d, e, a, g, and b from Saccharomyces cerevisiae, τ, α, βy, δ and e from rat liver, and TFIID, TFIIB, RAP30/74 or TFIIF, BTF2 or TFIIH, and TFIIE from human cells. In addition to these factors, other proteins have been shown to stimulate either the initiation or elongation stages of transcription by RNA polymerase II. One such factor, designated TFIIA, has been purified from both Saccharomyces cerevisiae and mammalian cells and appears to promote assembly of the preinitiation complex. Although TFIIA is not essential for initiation, several lines of evidence suggest that it functions to increase the number of productive preinitiation complexes formed at a variety of promoters in vi tro. Although considerable progress has recently been achieved identifying and characterizing transcription factors that support a basal level of transcription by RNA polymerase II, significantly less information is available on transcription factors that control the efficiency of transcription initiation or RNA chain elongation. Such activities play an important role in regulating gene expression. Only two transcription factors that influence RNA chain elongation have been identified and characterized with a high degree of certainty. The general initiation factor TFIIF (RAP 30/74) from Drosophila and human cells has been shown to stimulate the rate of RNA chain elongation and to promote read-through by RNA polymerase at a variety of pause sites. Transcription factor SII has been shown to promote RNA polymerase read-through at intrinsic pause sites in a human histone gene, in the adenovirus genome, and at several other sites. A transcription factor designated YES was recently purified to apparent homogeneity from Saccharomyces cerevisiae . YES is composed of a single 115 kDa polypeptide and appears to stimulate the rate of RNA chain elongation by RNA polymerase on synthetic oligo(dC) -tailed DNA templates, although its existence is now in question. Additionally, a transcription factor designated TFIIX has been described. However, it has not yet been purified; thus, it is not yet clear how it is related to other better characterized elongation factors. Many of the initiation factors and one or more elongation factors (e.g., TFIIF) are commercially available from most suppliers of biological enzymes (e.g., Upstate Biotechnology, Promega Corp., and Santa Cruz Biotechnology, Inc.). The ability of RNA polymerase to form an active complex in vitro capable of specifically initiating and efficiently elongating RNA is vital to the development of genetically engineered industrial systems for the production of recombinant products. Furthermore, other as yet unknown elongation factors hold the key to many cellular functions. Thus, the ability to manipulate the transcription of genes is necessary to overcome many hurdles in genetic engineering and will be required to cure several human diseases. One such area which relies upon elucidation of genetic mechanisms is the effort to understand the etiology and treatment of diseases caused by viruses. For example, one of the most intensive efforts in recent years has focused on the HIV virus which causes Acquired Immune Deficiency Syndrome (AIDS) . It has been reported that the HIV encoded Tat protein recruits unknown cofactors to the HIV-l LTR TAR element (Madore, et al. , J Virology 67: 3703 (1993)) thereby inducing activation of viral gene expression. There is reason to believe the unknown co-factors are likely to be elongation factors, and thus, further identification of elongation factors are important in elucidating genetic means for treating AIDS. In addition, as the HIV Tat protein is itself believed to be an elongation factor, cellular elongation factors will be important components of assay systems designed to identify pharmacologic agents that interfere with the activity of the HIV Tat protein. (Rosen, C.A., AIDS Research and Human Retroviruses 8: 175-181 (1992)) . Elongation factors are also believed to be involved with the repair of actively transcribed genes. Transcribed genes are repaired on a priority basis because the resulting translation product would likely be either a mutated full-length product or a truncated product (due to premature termination of transcription) . Elongation factors would be a likely signal for repair systems such as ERCC 3 because they are one of the few enzymes which are associated with DNA only when mRNA is actually being elongated. Elucidation of this signal could result in a treatment for certain repair deficiency diseases such as xeroderma pigmentosum and Cockaynes syndrome. Elongation factors are also likely to be involved in the regulation of a number of cellular genes including the proto oncogene C-myc and genes involved in the cellular stress response. In brief, the presence or absence of these elongation factors controls the rate of transcription of many genes and their absence can even prevent continued transcription. They are certainly involved in the coordination of transcription with other cellular functions. However, despite the advances made to date in the field of genetic engineering, there is a continuing need for novel factors which affect the rate and efficiency of transcription. SUMMARY OF THE INVENTION A novel RNA polymerase transcription factor, designated Elongin or SIII, is provided. Increasing the available amount of this protein in transcription systems significantly increases the rate of transcription. In another embodiment the present invention is directed to a method for isolating Elongin from eukarotic cells. For example, brain and liver cells can be used as sources of this novel transcription factor. In another embodiment, the present invention is directed toward the cDNAs encoding both the rat and human Elongin subunits of -15, -18 and -110 kDa. In still another embodiment the present invention is directed toward recombinantly produced Elongin as well as the vectors and transformation systems which make that possible. These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and appended claims. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a preferred purification scheme of RNA polymerase transcription factor SIII (Elongin) from rat liver, where P-cell represents phosphocellulose and φ represents a phenyl group. Fig. 2 is a graph depicting the results of runoff transcription assays which illustrate Elongin stimulation of transcription in a dose-dependent manner. Fig. 3 is a graph depicting the transcriptional activity of recombinantly produced Elongin. In some instances certain subunits were omitted. DETAILED DESCRIPTION The following description provides details of the manner in which the embodiments of the present invention may be made and used in order to achieve the separation, purification and characterization of an RNA polymerase elongation factor (Elongin) which was not previously known. Also included is a description for the recombinant production of this factor. These descriptions, while exemplary of the present invention, are not to be construed as specifically limiting the invention, and such variations which would be within the purview of one skilled in this art are to be considered to fall within the scope of this invention. Definitions: The abbreviations used are: AMP-PNP, adenyl-5'-yl imidodiphosphate; PMSF, phenylmethylsulfonyl fluoride; TFA, trifluoroacetic acid; HPLC, high pressure liquid chromatography; DTT, dithiothreitol; HEPES, N- [2- hydroxyethyl]piperazine-N' - [2-ethanesulfonic acid]; SDS, sodium dodecyl sulfate; EDTA, ethylenediaminetetraacetic acid; AdML, adenovirus 2 major late; USF, upstream stimulatory factor; and MLTF, major late transcription factor. "~" means approximately. Whenever a nucleic acid is referred to, either directly or inferentially, it may be meant to include the nucleic acid in both the sense and anti-sense orientations. A new RNA polymerase transcription factor has now been isolated. This transcription factor can be used to increase the rate of transcription by stimulating synthesis by RNA polymerase. Several lines of evidence demonstrate that this transcription factor, designated Elongin or SIII, is a heterotrimeric protein composed of approximately 110, 18, and 15 kDa subunits. These are: (i) polypeptides of approximately 110, 18, and 15 kDa compose at least about 90% of the protein in the most highly purified preparations of Elongin; (ii) Elongin activity co-chromatographs with approximately 110, 18, and 15 kDa polypeptides during both ion-exchange and hydrophobic interaction HPLC; (iii) Elongin activity can be reconstituted by recombining the approximately 110, 18, and 15 kDa polypeptides isolated by reverse phase HPLC; and (iv) based on the results of gel filtration and sedimentation experiments, Elongin exhibits a native molecular mass of about 140 kDa, consistent with the idea that it contains a single copy of each of the three polypeptides. Elongin is structurally distinct from the TATA factor (τ/TFIID) , its DNA binding subunit (the TATA Binding Protein or TBP) , and general initiation factors α(TFIIB), βy(TFIIF), δ(BTF2/TFIIH) , and e(TFIIE). Nor will it replace any of these factors in reconstitution of promoter-specific initiation. In addition, its polypeptide composition differs from that of TFIIA which stimulates transcription initiation by RNA polymerase. Elongin also appears to be distinct from elongation factors designated SII and TFIIX. Mammalian SII is composed of a single, 38 kDa polypeptide, and thus differs structurally from Elongin. TFIIX, on the other hand, has thus far been defined only as an activity present in a chromatographic fraction from HeLa cells. However, while both Elongin and the TFIIX activity bind tightly to phosphocellulose and are eluted between 0.5 and 1.0 M KCI, Elongin flows through DEAE cellulose at 0.1 M KCI (data not shown), while TFIIX binds this resin and is eluted between 0.1 and 0.5 M KCI. The following examples describe experiments investigating the functional properties of Elongin. These indicate that Elongin stimulates promoter specific transcription by increasing the rate of RNA chain elongation by RNA polymerase. The following observations argue that Elongin exerts its activity directly on the elongation complex: (i) in pulse chase experiments, Elongin does not need to be present during preinitiation complex formation or transcription initiation in order to stimulate transcription; and (ii) Elongin stimulates the rate of RNA chain elongation during transcription of double stranded oligo dC-tailed templates. In this respect, the activity of Elongin resembles that of the well-characterized transcription elongation factor SII and the elongation stimulatory activity of TFIIF. By several criteria, the functional properties of Elongin more closely resemble those of TFIIF than those of SII. SII has been shown to suppress RNA polymerase pausing in response to intrinsic signals found in a variety of genes, including the human histone H3.3, the Adenovirus major late, and murine adenosine deaminase genes, but it does not appear to produce a general increase in the rate of RNA chain elongation. In contrast, TFIIF does not release polymerase paused at intrinsic pause sites, but it is reported to increase the rate of RNA chain elongation. Under appropriate reaction conditions, RNA polymerase can achieve "physiological," elongation rates of 1200-1500 nt/min in the presence of the TFIIF factor. Like TFIIF, Elongin is capable of stimulating the overall rate of RNA chain elongation under a variety of experimental conditions. In the presence of 500 μM NTPs and either Elongin or recombinant βy(TFIIF), RNA polymerase elongates RNA chains at about 500 nucleotides/min, consistent with previously reported rates of TFIIF-stimulated elongation measured at 30°C. Elongin is capable of strongly stimulating the rate of elongation of promoter-specific transcripts in the presence of βy(TFIIF) concentrations that just saturate the initiation reaction. Present data also indicates that Elongin does not promote read-through by polymerase paused at the intrinsic H3.3 pause site. In addition, unlike SII, Elongin does not promote cleavage of nascent RNA molecules by paused or stalled RNA polymerase. SII and Elongin, therefore, are members of different classes of transcription elongation factors and may perform complementary functions in the regulation of eukaryotic messenger RNA synthesis. In summary, RNA polymerase transcription factor SIII (Elongin) is defined as a protein, which is composed of subunits with electrophoretic mobilities corresponding to relative molecular masses of -110 kDa (Elongin A) , -18 kDa (Elongin B) and -15 kDa (Elongin C) and which is capable of increasing the rate at which purified RNA polymerase incorporates ribonucleoside triphosphates into RNA chains. All steps in the purification of Elongin are preferably carried out in buffer maintained at about pH 6.5-8.5 unless otherwise indicated. Elongin was purified from a crude nuclear fraction from rat liver, although Elongin can be present in any nucleated cell. This crude nuclear fraction contains, in addition to Elongin, a large amount of contaminating DNA and RNA as well as many other proteins and enzymes. The procedure summarized below allows separation of Elongin from these contaminants. The purified Elongin represents <~0.001% (by weight of protein) of the starting material. Because many nuclear proteins are bound tightly to nucleic acid or other insoluble nuclear components at low ionic strength, in one embodiment of acquiring Elongin, nuclei were extracted with a moderate concentration of ammonium sulfate (NH 4 ) 2 S0 4 to solubilize as much nuclear protein as possible. Insoluble material was typically removed by centrifugation at >20,000 x g, although other methods known to one skilled in the art can be used. Ammonium sulfate precipitation was used as the preferred initial fractionation step. Following ammonium sulfate fractionation, Elongin activity was present in a fraction of protein that was insoluble in about 40% ammonium sulfate. This protein fraction was further fractionated by cation exchange chromatography. Fractions containing Elongin activity were pooled, and the Elongin further purified using gel exclusion chromatography, or any other procedure which separates proteins according to molecular size. Active fractions from gel exclusion chromatography were pooled and preferably applied to a hydrophobic interaction chromatography resin. The hydrophobic interaction chromatography resin was eluted with a descending concentration gradient of ammonium sulfate. Active fractions were pooled and preferably applied to a cation exchange resin. Active fractions prepared using this or a similar combination of fractionation steps (the order is not necessarily critical) contained three major polypeptides with electrophoretic mobilities corresponding to relative molecular masses of -110 kDa, -18 kDa, and -15 kDa. These three polypeptides were further purified and separated from one another by reverse phase HPLC. Prior to reverse phase HPLC, the protein was denatured in a solution containing urea, guanidine hydrochloride, trifluoroacetic acid, and acetonitrile. This procedure allowed clean separation of the three polypeptides, which each eluted as a single, sharp peak. When the Elongin fraction was loaded onto the reverse phase column without prior denaturation with urea and guanidine hydrochloride, Elongin A eluted from the column in multiple broad peaks, which most likely represent different conformers of the polypeptide. Following reverse phase separation of the three Elongin polypeptides, they were mixed together and renatured in various combinations. To renature the Elongin polypeptides, volatile solvents from reverse phase fractionation were removed by lyophilization. Dried protein was dissolved in a high concentration of the chaotropic agent guanidine hydrochloride and then rapidly diluted in a pH 7.9 "refolding" buffer containing a moderate concentration of salt, a reducing agent, glycerol, and a low concentration of ZnS0 4 , which may promote proper folding of one or more of the Elongin polypeptides. To remove guanidine hydrochloride, the protein solution was dialyzed for several hours against refolding buffer. After carrying out the above protocol, various combinations of the renatured Elongin A, B and C polypeptides were assayed for their abilities to stimulate transcription elongation by RNA polymerase II. The results of this experiment indicated that all three polypeptides are required for full activity of Elongin. Elongin can also be acquired through the utilization of genetic engineering techniques. The methods required to develop an expression system from an isolated protein are known in the art. (Old and Primrose, Pτ-in<-?iples of Gene Manipulation, 4th. ed. (1989) and Sambrook et al., Molecular Cloning, 2ed. , Cold Spring Harbor Laboratory Press, (1989) . The cDNAs for the rat derived Elongin C, B and A subunits have been sequenced (SEQ ID NO: 1, SEQ ID NO: 3, and SEQ ID NO: 5, respectively) as well as the amino acid sequences deduced from those cDNA sequences (SEQ ID NO: 2, SEQ ID NO: 4, and SEQ ID NO: 6, respectively) . The methods used are described in Example 2 and are standard procedures in the art. For isolation of cDNAs encoding Elongin C and Elongin B, sense and antisense nucleotide sequences based on tryptic peptides of particular subunits were used as primers for PCR. The PCR products were then subcloned to produce plasmid vectors containing partial cDNA sequences. Those cDNAs encoding the complete subunits were obtained by screening rat cDNA libraries using radioactive probes derived from these plasmid vectors by asymmetric PCR. For isolation of cDNAs encoding the Elongin A, a rat cDNA library was screened with degenerate oligonucleotides encoding Elongin A tryptic peptide sequences to identify candidate cDNAs. Bona fide Elongin A cDNA clones were identified by PCR screening, using a primer whose sequence was based on an Elongin A tryptic peptide sequence. Although these methods worked for their intended purposes, numerous variations which will occur to one skilled in the art, are possible to achieve the same result. The individual subunits were then produced with M13 expression vectors as described in Example 3. Any of the known expression methods would be suitable substitutions for this vector system, including eukaryotic systems such as baculovirus. The three subunits can then be recombined into the quaternary structure with the expected activity (See Example 4) . Example 5 details the methods used to obtain the cDNA for the human Elongin C subunit (SEQ ID NO: 7; amino acid sequence, SEQ ID NO: 8) , the human Elongin B subunit (SEQ ID NO: 9; amino acid sequence, SEQ ID NO: 10) and the human Elongin A subunit (SEQ ID NO: 11; amino acid sequence SEQ ID NO: 12) . Briefly probes were prepared from the corresponding rat subunit cDNAs. These probes were then used in PCR or other methods to obtain the human sequences from either a human peripheral blood lymphocyte or human umbilical vein endothelial cell cDNA library. Again, there are various ways known to one skilled in the art to obtain this end. As Elongin cDNA has now been found in human peripheral blood lymphocyte, human umbilical vein endothelial cell, rat brain and rat liver cDNA libraries, it is expected that Elongin is a ubiquitous protein, involved with transcription in most cells. Therefore, it is expected that Elongin cDNA can be isolated from many other mammalian cDNA libraries. In one embodiment of the invention, probes are made corresponding to sequences of the cDNAs which are complimentary to the mRNA for Elongin. These probes can be radioactively or non-radioactively labeled in a number of ways well known to those skilled in the art for use in screening for Elongin related proteins or diagnostics. The probes can be made of various lengths. Factors such as stringency and GC content may influence the desired probe length for a particular application. Generally, they can be from 10 nucleotides to the entire nucleic acid coding for a given subunit. EXAMPLE 1 Isolation, Purification and Detection of Elongin (See Fig. 1 and Table I) Materials Male Sprague-Dawley rats (200-300 gm) were purchased from SASCO. Unlabelled ultra pure ribonucleoside 5'- triphosphates and dATP were from Pharmacia LKB Biotechnology, Inc. (Piscataway, N.J.). AMP-PNP was obtained from Sigma Chemical Co. (St. Louis, MO) or Pharmacia. [α- 32 P] CTP (>650 Ci/mmol) and [ - 32 P] ATP (>650 Ci/mmol) were obtained from ICN Biomedicals, Inc. (Costa Mesa, CA) . PMSF, antipain, and heparin were from Sigma Chemical Co. Leupeptin was obtained from Boehringer Mannheim Corp. (Indianapolis, IN) . Bovine serum albumin (Pentex fraction V) was obtained from ICN ImmunoBiologicals. Glycerol (spectranalyzed grade) was from Fisher Scientific (Pittsburgh, PA) . Schwarz/Mann ultrapure sucrose and ammonium sulfate were from ICN Biomedicals, Inc. For reverse-phase chromatography, acetonitrile and trifluoroacetic acid (HPLC/Spectro grade) and urea and guanidine hydrochloride (Sequanal grade) were from Pierce (Rockford, IL) . Chromatography and Buffers Phosphocellulose (Pll) and DEAE-cellulose (DE51) were purchased from Whatman, Inc. (Clifton, N.J.). 4000SW Spherogel TSK, Spherogel TSK phenyl-5-PW, and Spherogel TSK SP5-PW were obtained from Beckman Instruments, Inc. (Fullerton, CA) . HPLC was performed using a Beckman System Gold chromatograph. Buffer A was 20 mM HEPES-NaOH, pH 7.9, 1 mM EDTA, 1 mM DTT, 20% (v/v) glycerol, and 0.5 mM PMSF. Buffer B was 50 mM Tris-HCl, pH 7.9, 0.1 mM EDTA, 1 mM DTT, 20% (v/v) glycerol, and 0.5 mM PMSF. Buffer D was 40 mM HEPES-NaOH, pH 7.9, 0.5 mM EDTA, 1 mM DTT, and 10% (v/v) glycerol. Buffer E was 40 mM HEPES-NaOH, pH 7.9, 0.1 mM EDTA, 1 mM DTT, and 10% (v/v) glycerol. Buffer G was 40 mM HEPES-NaOH, pH 7.0, 0.5 mM EDTA, 1 mM DTT, and 10% (v/v) glycerol. Purification of Elongin Step 1. Preparation of the Nuclear Extract. A 0.33 M (NH 4 ) 2 S0 4 extract of crude rat liver nuclei was prepared from the livers of 300 male Sprague-Dawley rats as previously described (Conaway, J.W. and Conaway, R.C, J Biol Chem 264: 2357-2362 (1989)). All further operations were carried out at 4°C. Step 2: (NH 4 ) 2 S0 4 Fractionation. Solid (NH 4 ) 2 S0 4 (0.186 g/ml) was added slowly to the nuclear extract. After addition of lμl l.O N NaOH per gram of (NH 4 ) 2 S0 4 , the suspension was stirred an additional 30 min. The precipitate was collected by centrifugation at 12,000 x g for 45 min and then dissolved in Buffer B containing antipain and leupeptin at 10 μg/ml each (Fraction I) . Step 3: DEAE-cellulose (DE52) Chromatography. Fraction I was diluted with Buffer B to a conductivity equivalent to that of 0.1 M (NH 4 ) 2 S0 4 in Buffer B and then centrifuged at 7,500 x g for 15 min. The supernatant was mixed with 1.0 liter of DEAE-cellulose pre-equilibrated with Buffer B containing 0.1 M (NH 4 ) 2 S0 4 in a 10.5-cm diameter column. The slurry was allowed to sit for 45 min with occasional stirring and then filtered at 1.0 liter/hour. The column was washed at the same flow rate with Buffer B containing 0.1 M (NH 4 ) 2 S0 4 until the eluate contained <0.05 mg/ml protein. Fractions containing protein were pooled and dialyzed against Buffer A to a conductivity equivalent to that of 0.1 M KCI in Buffer A (Fraction II) . Step 4: Phosphocellulose (Pll) Chromatography. Fraction II was centrifuged at 4,000 x g for 10 min, and the supernatant was mixed with 800 ml of phosphocellulose pre-equilibrated with Buffer A containing 0.15 M KCI in a 10.5-cm diameter column. The slurry was allowed to sit for 45 min with occasional stirring and then filtered at 500 ml/hour. The column was washed at the same flow rate with Buffer A containing 0.5 M KCI until the eluate contained less than 0.05 mg/ml protein. Transcription activity was eluted stepwise at one packed column volume/ hour with Buffer A containing 1.0 M KCI. Fractions of one-fifth column volume were collected, and those containing activity were pooled and dialyzed against Buffer A containing 0.5 M (NH 4 ) 2 S0 4 for 2.5 hours (Fraction III) . Step 5: TSK 4000SW HPLC. Solid (NH 4 ) 2 S0 4 (0.3 g/ml) was added slowly to Fraction III with stirring. 1 μl of l.O N NaOH per gram of (NH 4 ) 2 S0 4 was then added, and the suspension was stirred an additional 30 min. The precipitate was collected by centrifugation at 15,000 x g for 90 min and dissolved to a final volume of 5 ml in Buffer G. The solution was dialyzed against Buffer G until the conductivity was equivalent to that of Buffer G in 0.5 M (NH 4 ) 2 S0 4 and then centrifuged at 80,000 x g for 20 min. The resulting supernatant was applied to a 4000SW Spherogel TSK HPLC column (21.5 x 600 mm) pre- equilibrated in Buffer G in 0.5 M KCI. The column was eluted at 4 ml/min and 5 ml fractions were collected. Active fractions were pooled (Fraction IV) . Step 6: TSK Phenyl-5-PW HPLC. Fraction IV was diluted with an equal volume of Buffer E containing 2.0 M (NH 4 ) 2 S0 4 , and then centrifuged at 60,000 x g for 20 min. The resulting supernatant was applied to a Spherogel TSK phenyl-5PW column (21.5 x 150 mm) pre-equilibrated in Buffer E containing 1.0 M (NH 4 ) 2 S0 4 . Transcription activity was eluted at 5 ml/min with a 500 ml linear gradient from 1.0 M (NH 4 ) 2 S0 4 in Buffer E to Buffer E. Ten ml fractions were collected, and the active fractions, which eluted between 0.45 to 0.3 M (NH 4 ) 2 S0 4 , were pooled and dialyzed against Buffer D containing 0.05 M KCI to a conductivity equivalent to that of Buffer D in 0.1 M KCI (Fraction V) . Step 7: TSK SP-5-PW HPLC. Fraction V was centrifuged at 60,000 x g for 20 min, and the supernatant was applied to a Spherogel TSK SP-5-PW column (7.5 x 75 mm) pre-equilibrated in Buffer D containing 0.1 M KCl. The column was eluted at 1 ml/min with a 50 ml linear gradient from 0.1 to 0.8 M KCl in Buffer D. One ml fractions were collected. Transcription activity eluted between 0.31 and 0.38 M KCl (Fraction VI) . Purification of Elongin Polypept-ide by Reverse Phasp. Chromatography Reverse phase narrow bore HPLC was performed using an Ultra-fast Micro Protein Analyzer (Michrom BioResources, Pleasanton, CA) . An aliquot (-50 μg) of Elongin (Fraction VI) was diluted 1:1 with "magic mix", (Nugent, et al., J Chromatography 443: 381-397 (1988)), denaturant (4.0 M guanidine hydrochloride, 4.0 M urea, 7.5% acetonitrile, 0.15% TFA), and 0.2% Zwittergent ZC-8 (Calbiochem) and applied to a 2.1 x 50 mm PLRP-S (lOOoA pore size; 8μ particle size) reverse phase HPLC column (Michrom BioResources) pre-equilibrated at 54°C in 20% eluent B (90% acetonitrile, 0.09% TFA, and 0.03% Zwittergent ZC-8) and 80% eluent A (2% acetonitrile, 0.1% TFA, and 0.03% Zwittergent ZC-8) . The column was developed at 0.4 ml/min with a 22 min linear gradient from 20% to 75% eluent B. Peaks of absorbance at 220 nm were collected manually. TABLE I Purification of Transcript: Lon Factor Elongin from Rat Liver SPECIFIC FRACTION PROTEIN VOLUME ACTIVITY 3 ACTIVITY YIELD (mg) (ml) (units) (units/mg) (%) I. Nuclear Extract 40% (NH 4 ) 2 S0 4 fraction 25,000 10 II. DEAE Cellulose (DE-52) 13,000 3550 III. Phosphocellulose (P-ll) 240 400 445,000 1,850 100 b IV. TSK-SW4000 70 35 287,000 4,100 65 to V. TSK-phenyl-5PW 4.2 60 56,300 to 13,400 13 VI. TSK-SP-5PW 0.35 6 182,000 519,000 41 15 a Runoff transcription assays performed as described on page 23 using the Eeo RI to Nde I fragment from pDN-AdML DNA as template. Following a 30 minute preincubation of RNA polymerase II, transcription factors, and DNA, runoff transcription was carried out for an additional 18 min in the presence of 50 μM ATP, 2 μM UTP, 10 μM CTP, 50 μM 20 GTP, and 10 μCi [ - 32 P] CTP. One unit is the amount of Elongin required to reconstitute half maximal runoff transcription. b 0verall yield is based on fraction III since Elongin activity could not be reliably measured in fractions I and II. Recovery of Elongin Activity Following Reverse Phase HPLH Fractions from reverse phase narrow bore HPLC were lyophilized until just dry using a Savant Speed-Vac (Savant Instruments, Farmingdale, N.Y.). Dried protein was resuspended in 5 μl of 6.0 M guanidine hydrochloride and left on ice for 30 min. Aliquots were then diluted to 50 μl with renaturation buffer (40 mM HEPES-NaOH, pH 7.9, 0.1 M KCl, 2 mM DTT, 50 μM ZnS0 4 , 0.1 mM EDTA, and 10% (v/v) glycerol) and left on ice an additional 90 min. Aliquots were then dialyzed for 2 hours against renaturation buffer lacking EDTA and DTT and stored at -80°C. Preparation of RNA Pol srasa TT and Transcription Factors RNA polymerase II (Serizawa, et al. , Proc Natl Acad Sci USA 89: 7476-7480 (1992)) the native rat TATA factor τ (Conaway et al., J Biol Chem 265: 7552-7558 (1990)) and transcription factor δ (BTF2) (Conaway, R.C. and Conaway, J.W., Proc Natl Acad Sci USA 86: 7356-7360 (1989); and Conaway, et al., J Biol Chem 267: 10142-10148 (1992)) were purified from rat liver as previously described. Recombinant yeast TFIID was expressed and purified as described (Conaway, et al., J Biol Chem 266: 7804-7811 (1991) ) from bacterial strain N5151 containing the plasmid pASY2D (Schmidt, et al., Proc Natl Acad Sci USA 86: 7785-7789 (1989)). Recombinant rat α(TFIIB) (Tsuboi, et al., Nucleic Acids Res 20: 3250 (1992)) and recombinant human TFIIE (Peterson, et al., Nature 354: 369-373 (1991)) were prepared as described, except that the 56 kDa subunit of TFIIE was expressed in BL2KDE3). Recombinant βy(TFIIF) was purified by phosphocellulose chromatography (Conaway, J.W. and Conaway, R.C, J Biol Chem 264: 2357-2362 (1989)) of whole cell extracts prepared from SF21 cells co-infected with recombinant baculoviruses encoding the βy(TFIIF) subunits, human RAP74 (Aso, et al., Nature 355: 461-464 (1992); and Finkelstein, et al., Nature 355: 464-467 (1992)) and rat RAP30 (Garrett, et al., J Biol Chem 267: 23942-23949 (1992) ) . Recombinant viruses were constructed using the BacPAK6 baculovirus expression system (Clontech Laboratories, Inc., Palo Alto, CA) . Assay of Runoff Transcript on Unless indicated otherwise, preinitiation complexes were assembled as described (Conaway, et al., J Biol Chem 262: 8293-8297 (1987)) by preincubation of 100 ng of Νde I-digested pDΝ-AdML, (Conaway R.C. and Conaway, J.W., J Biol Chem 263: 2962-2968 (1988)) or 100 ng of Νde I- digested pΝ 4 (Lorch, et al., Cell 49: 203-210 (1987)) and approximately 10 ng of recombinant (TFIIB), 10 ng of recombinant βy(TFIIF) , 7 ng of recombinant human TFIIE, 40 ng of δ(BTF2) (Fraction VI), 60 ng τ (Fraction V) or 50 ng of recombinant yeast TFIID (AcA 44 fraction) , and 0.01 unit of RNA polymerase II. Transcription was initiated by addition of 7 mM MgCl 2 and 50 μM ATP, 2 μM UTP, 10 μM CTP, 50 μM GTP and 10 μCi [ - 32 P] CTP. After incubation at 28°C for 18 min runoff transcripts were analyzed by electrophoresis through 6% polyacrylamide/7.0 M urea gels. Transcription was quantitated by densitometry of autoradiograms using an LKB UltroScan XL laser densitometer. flnrrose Gradient Sedimentation Sedimentation was performed in 2 ml linear sucrose gradients (15-30% [v/v] containing 20 mM HEPES-NaOH, pH 7.9, 1 mM EDTA, 1 mM DTT, and 0.4 M KCl). Centrifugation was carried out at 55,000 rpm and 4°C in the TLS55 rotor of a Beckman TL100 ultracentrifuge. Fractions (2 drops) were collected from the bottom of tubes through a 20- gauge needle. Protein Determination Protein concentrations were determined using the protein dye assay (Bio-Rad Laboratories, Hercules, CA) with bovine serum albumin as the standard. Detection of Elongin Elongin-dependent transcriptional stimulation is readily detected if any of the four ribonucleoside triphosphates are present at limiting concentrations. This property of Elongin was exploited to purify it to apparent homogeneity from rat liver nuclear extracts. Elongin was assayed by its ability to reconstitute synthesis of a 250-nucleotide runoff transcript from the core region of the AdML promoter in the presence of a limiting concentration of UTP and saturating amounts of RNA polymerase II, initiation factors α(TFIIB), βy(TFIIF), δ(BTF2/TFIIH) , and e(TFIIE), and either the native rat TATA factor τ or recombinant yeast TFIID. The standard template was pDN-AdML (Conaway, R.C. and Conaway, J.W., J Biol Chem 263: 2962-2968 (1988)), which includes AdML core promoter sequences, but which lacks the upstream sequences that mediate stimulation of transcription by USF/MLTF. Elongin was purified to near homogeneity from a 0.33 M (NH 4 ) 2 S0 4 extract of crude rat liver nuclei by ammonium sulfate fractionation, followed by chromatography on successive DEAE-cellulose, phosphocellulose, TSK 4000SW, TSK phenyl-5-PW, and TSK SP-5-PW columns. Elongin activity was first reliably measured in the phosphocellulose fraction (Fraction III) . Approximately 350 μg of Elongin (Fraction VI) can be purified from ~3 kg of rat liver. The overall yield from Fraction III was approximately 40%. The more than 100% yield of Elongin activity on TSK SP-5-PW was most likely due to removal of inhibitors present in Fraction V. Elongin is a multi-subunit protein composed of -110, -18, and -15 kDa polypeptides, Elongin A, B and C, respectively. Analysis of the TSK SP-5-PW column fractions by SDS-polyacrylamide gel electrophoresis revealed that polypeptides with apparent molecular masses of approximately 110, 18, and 15 kDa co-chromatographed with transcriptional stimulatory activity and accounted for more than 90% of the protein in the active fractions. Transcriptional stimulatory activity did not elute from TSK SP-5-PW in a symmetrical peak. The bulk of activity was recovered in fractions 25 and 26, but significant activity eluted as a shoulder on the leading edge of this peak. The two small polypeptides appeared to be present in higher molar amounts (relative to the large polypeptide) in fractions 25 and 26 than in the earlier eluting fractions. In addition, it was observed that the Elongin subunits also co-chromatographed with transcriptional activity when Elongin was analyzed by hydrophobic interaction chromatography on TSK phenyl-5-PW (data not shown) . To determine which polypeptides were required to reconstitute Elongin activity, the protein in an aliquot of fraction 26 from the TSK SP-5-PW column was denatured and fractionated by reverse phase HPLC. The Elongin subunits were each recovered in apparently homogeneous form. The polypeptides were renatured alone or in combination with other polypeptides and assayed for activity. Transcriptional activity was recovered only when all three polypeptides were combined and renatured together. It could not be reconstituted with any single polypeptide renatured independently or with any combination of independently renatured polypeptides. In addition, transcriptional activity could not be recovered when pairs of polypeptides were renatured together. However, in studies using recombinant subunits (See Example 4) a slight stimulation of transcription was observed with Elongin A alone; the combination of Elongin A and Elongin C had somewhat more activity and maximal activity depended on the presence of Elongin A, B and C. Thus, it appears that Elongin A alone exhibits a low, basal level of transcription while both the Elongin B and Elongin C strongly stimulate this activity. As measured by TSK 4000SW size exclusion HPLC, Elongin has a Stokes radius of -47A. By sucrose gradient sedimentation, Elongin has a sedimentation coefficient of -6 S. Assuming a partial specific volume of 0.725 ml/g, Elongin has an apparent native molecular mass determined by the method of Siegel and Monty (Siegel, L.M. and Monty, K.J., Biochim Biophys Acta 112: 346-362 (1966)) of -140 kDa, consistent with Elongin being a heterotrimer composed of a single copy each of the -110, -18, and -15 kDa polypeptides. EXAMPLE 2 Isolation of cDNA Clones Encoding Rat Elongin Method for Generating cDNA From -15 kDa Elongin finhnni - Elongin C Approximately 300 pmol of Elongin C, isolated by reverse phase HPLC, was digested with trypsin. The NH 2 terminal sequences of four tryptic peptides (I-IV) , determined by automated Edman microsequencing, were as follows: I, NH 2 -LISSDGHEFIVKR-COOH (SEQ ID NO:13);II, NH 2 -AMLSGPGQFAENETNEVNFR-COOH (SEQ ID NO:14); III, NH 2 - VCMYFTYK-COOH (SEQ ID NO:15);IV, NH 2 - YTNSSTEIPEFPIAPEIALELLMAANFLD-COOH (SEQ ID NO:16) . A partial cDNA encoding residues 51-97 of the Elongin C was isolated by polymerase chain reaction (PCR) using as primers the sense and antisense degenerate oligonucleotides 5' -CARTTYGCNGARAAYGARAC-3 • (SEQ ID NO:17) and 5'-GGNGCDATNGGRAAYTCNGG-3' (SEQ ID NO:18) encoding residues 8 through 14 of tryptic peptide II and residues 9 through 15 of tryptic peptide IV, respectively. PCR was performed for 30 cycles of 1 min at 94°C, 1 min at 46°C, and 2 min at 72°C with 1.5 mM MgCl 2 , 0.25 mM dNTPs, 2.5 units of Taq polymerase, 0.02 A 260 unit of each primer, and -6 x IO 6 pfu of a rat liver λgtll cDNA library (Clontech) . PCR products encoding Elongin C polypeptide sequences were identified by Southern blotting, using as probe the 5'- 32 P-labeled degenerate oligonucleotide 5 ■ -ACNAAYGARGTNAAYTTYMG-3' (SEQ ID NO:19), which encodes residues 14 through 20 of tryptic peptide II, isolated by preparative polyacrylamide gel electrophoresis, and subcloned by blunt end ligation into pBluescript KS(-). Bacteria harboring a recombinant plasmid (pKGl) carrying the partial Elongin C cDNA were identified by colony hybridization using the same 5'- 32 P-labeled degenerate oligonucleotide as probe. cDNAs encoding the complete Elongin C polypeptide were obtained by screening rat liver and rat brain λ ZAP II cDNA libraries (Stratagene, La Jolla, CA) with an internally labeled, single stranded DNA probe synthesized by asymmetric PCR, using pKGl as template. pBluescript SK(-) phagemids containing cDNA inserts were rescued with helper phage and sequenced by the dideoxy chain termination method using a Sequenase kit (United States Biochemical Corp., Cleveland, OH). Two overlapping clones were combined to generate the full length rat Elongin C coding sequence (SEQ ID N0:1, nucleotide sequence; SEQ ID NO:2, amino acid sequence) . Method for Generating cDNA From -18 kDa Elongin Subunit - Elongin B Approximately 300 pmol of Elongin B was isolated by reverse phase HPLC (Bradsher, et al., J Biol Chem 268: 25587-25593 (1993a) ) . After reduction, S- carboxyamidomethylation, and digestion with trypsin, the resultant mixture was further fractionated by microbore HPLC. Optimal peptides were determined by differential UV absorbance and matrix-assisted laser desorption mass spectrometry (Lasermat; Finnigan-MAT, San Jose, CA) and submitted to automated Edman microsequencing (Lane, et al., J Prot Chem 10: 151-160 (1991)). The N-terminal sequences of two tryptic peptides (I and II) were obtained and were as follows: I, LYKDDQLLDDGKTLGECGFTSQTARPQ(A) (P) (SEQ ID NO:20) and II, ADDTGEALRIEPFSSPPELPDVMKPQDSG.G] (S)AN[E] (SEQ ID NO:21). A partial Elongin B cDNA was isolated from a rat liver λgtll cDNA library (Clontech) by PCR, using as primers the sense and antisense degenerate oligonucleotides 5'- TNTA(Y)AA(R)GA(Y)GA(Y)CA(R) (Y)T-3' (SEQ ID NO:22) and 5' - TGNGG(Y)TTCATNAC(R)TCNGG-3' (SEQ ID NO:23), which encode portions of tryptic peptide I and tryptic peptide II, respectively (R is A or G; Y is C or T; N is A, C, G, or T) . PCR was performed for 30 cycles of 1 min at 94°C, 1 min at 46°C, and 2 min at 72°C with 1.5 mM MgCl 2 , 0.25 mM dNTPs, 2.5 units of Taq polymerase, and 0.02 A 260 unit of each primer. PCR products encoding Elongin B polypeptide sequences were identified by Southern blotting using as probe the 5' - 32 P-labeled degenerate oligonucleotide 5'- GCNGA(Y)GA(Y)ACNTT(Y)GA(R)GC-3' (SEQ ID NO:24) which encodes residues 1-7 of tryptic peptide I, isolated by preparative polyacrylamide gel electrophoresis and subcloned by blunt-end ligation into pBluescript KS(-) . Bacteria harboring the recombinant plasmid (pKG2) carrying the partial Elongin B cDNA were identified by colony hybridization using the same 5' - 3 P-labeled degenerate oligonucleotide as probe. A cDNA encoding the complete Elongin B polypeptide was obtained by screening a rat brain λZAP II cDNA library (Stratagene, La Jolla, CA) with an internally labeled, single-stranded DNA probe synthesized by asymmetric PCR (McCabe, P.C, PCR Protocols : A Guide to Methods and Applications. Innis, et al., eds. (San Diego: Academic Press), pp. 76-83 (1990)) using pKG2 as template. Bluescript SK(-) phagemids containing cDNA inserts were rescued with VCS- M13 interference-resistant helper phage (Stratagene) and sequenced by the dideoxy chain-termination method using a Sequenase kit (United States Biochemical Corp.). The Elongin B nucleotide sequence is given in SEQ ID NO:3, and the corresponding amino acid sequence is listed in SEQ ID NO:4. Method for Generating cDNA From -110 kDA F.longin Subunit - Elongin A Approximately 300 pmol of Elongin A was isolated by reverse phase HPLC (Bradsher, et al., J Biol Chem 268: 25587-25593 (1993)). After reduction, S- carboxyamidomethylation, and digestion with trypsin, the resultant mixture was further fractionated by microbore HPLC. Optimal peptides were determined by differential UV absorbance and matrix-assisted laser desorption mass spectrometry (Lasermat; Finnigan-MAT, San Jose, CA) , and then submitted to automated Edman microsequencing, (Lane, et al., J " Prot Chem 10: 151-160 (1991)). The NH 2 terminal sequence of two trypyic peptides (I and II) were as follows: I, DVPQQEEEAEGNYQESWQASGSQPY(Y) (P)EHR (SEQ ID NO:25) ; II, ANENKSDKLQPAGAEPTRP (SEQ ID NO:26) . Two oligonucleotide "guessmer" probes were designed according to human codon usage bias. At some positions, inosine (I), was used instead of a mixture of four nucleotides. Primer 1, which is the complement of a sequence encoding amino acids 1-15 of tryptic peptide I, was 5'TCCTGGTAGTTICCTCIG CCTCCTCCTCCTGCTGIGGIACGTC (SEQ ID NO:27) , and Primer 2, which is the complement of a sequence encoding amino acids 10-17 of tryptic peptide two, was 5'CGGATCGTIGG(T/C) TCIGCICCIGCIGG(T/C)TG (SEQ ID NO:28) . A λGEM2 library constructed from size selected (>2kb) cDNA derived from rat brain (from Dr. Roger Wiegand, Monsanto Corp., Saint Louis, Mo.) was screened with 5' - 32 P-labeled Primer 1. Hybridization was at 37°C for 20 hours in 6X standard saline citrate (SSC) /IX Denhardt's solution/0.05% sodium pyrophosphate containing denatured salmon testes DNA at 100 μg/ml. Sixty-nine clones were isolated from 5 x IO 5 plaques. Phage clones derived from oligonucleotide screening were further screened by the polymerase chain reaction (PCR) method, using a T7 primer, CGTAATACGACTCACTATAGGG, (SEQ ID NO:29) , which hybridizes to a sequence in the λGEM2 vector, and Primer 2, respectively, as sense and anti- sense primers. PCR reactions were performed for 30 cycles of 1 min at 94°C, 1 min at 55°C, and 2 min at 72°C PCR reactions performed with eight of 69 phage clones yielded discrete products; the clone yielding the largest PCR product was selected and sequenced by the dideoxy chain termination method using a Sequenase kit. The Elongin A nucleotide sequence is given in SEQ ID NO:5 and the corresponding amino acid sequence is listed in SEQ ID NO:6. EXAMPLE 3 Expression of Rat Elongin in E. Coli Expression of Elongin C in E. rro71. Overexpression of Elongin C in E. coli was accomplished using an M13mpET bacteriophage expression system. The entire Elongin C coding sequence was introduced into M13mpET, which contains the complete pET T7 transcription/expression region. A 100-ml culture of E. coli strain JM109(DE3) (Promega) was grown to an OD 600 of 0.6 in SOB medium containing 2.5 mM MgCl 2 at 37°C with gentle shaking. Cells were infected with M13mpET carrying the full-length Elongin C cDNA at a multiplicity of infection of 10-20. After an additional 2 hours at 37°C, cells were induced with 0.4 mM isopropyl β-D- thiogalactoside, and the culture was incubated an additional 2.5 hours. Cells were harvested by centrifugation at 2000 x g for 10 min at 4°C, and inclusion bodies were prepared as previously described (Lin, K. & Cheng, S. BioTechniques 11: 748-753 (1991)), except that DNase and RNAse treatments were omitted. Inclusion bodies were solubilized by resuspension in 2 ml of ice-cold 50 mM Tris-HCl (pH 8.0) containing 6 M guanidine hydrochloride. The resulting suspension was clarified by centrifugation at 50,000 x g for 20 min at 4°C. Expression of Histidine-tagged Elongin R in E. col i Overexpression of histidine-tagged Elongin B was accomplished using an M13mpET bacteriophage expression system (Tan, et al., BioTechniques 16:824-828 (1994)). To make the expression vector ml3mpET-6Hpl8, which encodes pl8 with an 10 amino acid extension with the sequence MHHHHHHNVD (SEQ ID NO:30), the entire open reading frame encoded by the Elongin B cDNA was subcloned into the M13mpET-6H bacteriophage vector, (Tan, et al., BioTechniques 16: 824-828 (1994)). A 100 ml culture of E. coli strain JM109(DE3) was grown to an OD 600 of 0.6 in SOB medium containing 2.5 mM MgCl 2 at 37°C with gentle shaking. Bacteria were infected at a multiplicity of infection of 10-20. After an additional 2 hours at 37°C, cells were induced with 0.4 mM isopropyl β-D- thiogalactoside, and the culture was incubated an additional 2.5 hours. Bacteria were harvested by centrifugation at 2000 x g for 10 min at 4°C, and inclusion bodies were prepared as described, (Lin, K. and Cheng, S. BioTechniques 11: 748-753 (1991)), except that RNAase and DNAase treatments were omitted. Inclusion bodies were solubilized by resuspension in 2 ml ice-cold buffer containing 6 M guanidine hydrochloride, 40 mM Tris-HCl (pH 7.9), 10 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT. The resulting suspension was clarified by centrifugation at 50,000 x g for 20 min at 4°C and applied to a column containing 1 ml ProBond™ Metal- Binding Resin (Invitrogen) equilibrated with the same buffer. The column was washed with 10 ml of buffer containing 5.8 M guanidine hydrochloride, 40 mM Tris-HCl (pH7.9), 40 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT. Histidine-tagged Elongin B was then eluted with 3 ml of buffer containing 4 M guanidine hydrochloride, 40 mM Tris (pH 7.9), 300 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT. Expression of Hi stidine-tagged Elongin A in_J coli Overexpression of histidine-tagged Elongin A was accomplished using an M13mpET bacteriophage expression system (Tan, et al., Biorechnigues 16: 824-828 (1994)). To make the expression vector ml3mpET-6Hpll0, which encodes Elongin A with an 10 amino acid extension with the sequence MHHHHHHNVD (SEQ ID NO:31), the entire open reading frame encoded by the Elongin A cDNA was subcloned into the M13mpET-6H bacteriophage vector. A 100 ml culture of E. coli strain JM 109(DE3) was grown to an OD 600 of 0.6 in SOB medium containing 2.5 mM MgCl 2 at 37°C with gentle shaking. Bacteria were infected at a multiplicity of infection of 10-20. After an additional 2 hours at 37°C, cells were induced with 0.4 mM isopropyl β-D-thiogalactoside, and the culture was incubated an additional 2.5 hours. Bacteria were harvested by centrifugation at 2000 x g for 10 min at 4°C, and inclusion bodies were prepared as described (Lin, K. and Cheng, S. BioTechniques 11: 748-753 (1991)) except that the RNAase and DNAase treatments were omitted. Inclusion bodies were solubilized by resuspension in 2 ml ice-cold buffer containing 6 M guanidine hydrochloride, 40 mM Tris-HCl (pH 7.9), 10 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT. The resulting suspension was clarified by centrifugation at 50,000 x g for 20 min at 4°C and applied to a column containing 1 ml ProBond™ Metal- Binding Resin (Invitrogen) equilibrated with the same buffer. The column was washed with 10 ml of buffer containing 5.8 M guanidine hydrochloride, 40 mM Tris-HCl (pH 7.9), 40 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT. Histidine-tagged Elongin A was then eluted with 3 ml of buffer containing 4 M guanidine hydrochloride, 40 mM Tris (pH 7.9), 300 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT. EXAMPLE 4 Transcription Activity of Recombinant Elongin To reconstitute Elongin, -100 ng of recombinant histidine-tagged Elongin B and - 500 ng of recombinant histidine-tagged Elongin A, both in a solution of 4 M guanidine hydrochloride, 40 mM Tris-HCl (pH7.9), 300 mM imidazole (pH 7.9), 0.5 mM PMSF, and 1 mM DTT, were added to - 100 ng of lyophilized recombinant Elongin C, which had been prepared as described, (Garrett, et al., Proc Natl Acad Sci USA 91: 5237-5241 (1994)). This mixture was diluted - 15 fold with a buffer containing 40 mM HEPES-ΝaOH (pH 7.9), 100 mM KCl, 2 mM DTT, 50 μM ZnS0 4 , 0.1 mM EDTA, and 10% (v/v) glycerol and incubated 90 min on ice. Renatured proteins were dialyzed for 2 hours against the same buffer lacking EDTA and DTT. In some experiments, Elongin A, B, or C were omitted from the reconstitution mixture (See Fig. 3) . Renatured proteins were assayed for Elongin transcriptional activity as described (Bradsher, et al., J Biol Chem 268: 25594-25603 (1993b)); Garrett, et al., Proc Natl Acad Sci USA 91: 5237-5241 (1994)). Maximal stimulation of the rate of accumulation of full length runoff transcripts is dependent on the presence of Elongin A, B, and C A small stimulation of transcription is observed with Elongin A alone, but neither Elongin B or C nor a combination of Elongin C and Elongin B detectably stimulated transcription. Thus, Elongin C and Elongin B function as positive regulators of Elongin A activity. EXAMPLE 5 Isolation of cDNA Clones Encoding Human Elongin Isolation of a cDNA clone encoding human Elongin C A λZAPII library constructed with cDNA derived from peripheral blood lymphocytes (obtained from Drs. J. Culpeper and F. Lee, DNAX Research Institute, Inc., Palo Alto, CA) was screened with an internally labelled, single stranded probe containing rat Elongin C cDNA sequences. The probe was prepared by asymmetric PCR using as template a DNA fragment containing the entire rat Elongin C cDNA. Asymmetric PCR reactions were performed for 30 cycles of 1 min at 94°C, 1 min at 47°C, and 1 min at 72°C with 1.5 mM MgCl2, 50 μM dATP, 50 μM dGTP, 50 μM dTTP, 100 μCi [α- 32 P]dCTP (3000 Ci/mmole) and an anti-sense oligonucleotide primer, GCA GCG GAT CCT CAA CAA TCT AGG AAG TTC G (SEQ ID NO:32), which contains sequences derived from the 3' end of the rat Elongin C cDNA. Hybridization was at 50°C for 20 hrs in 5X standard saline citrate (SSC) /5X Denhardt's solution/0.1% SDS/10% dextran sulfate/100 mM NaHP0 4 /l ml/ml bovine serum albumin/100 μg/ml herring sperm DNA. Bluescript SK(-) phagemids containing cDNA inserts were rescued with VCS-M13 interference-resistant helper phage (Stratagene) and sequenced by the dideoxy chain-termination method using a Sequenase kit (United States Biochemical Corp.). The human Elongin C nucleotide sequence is given in SEQ ID NO:7 and the amino acid sequence is listed in SEQ ID NO:8. The human Elongin C cDNA encodes a protein with a predicted amino acid sequence identical to that of rat Elongin C These findings indicate that the human Elongin C mRNA is expressed in peripheral blood lymphocytes. Isolation of a cDNA clone encoding human Elongin B Oligonucleotide I: GCA ACG TCG ACA TGG ACG TGT TTC TCA TGA T (SEQ ID NO:33), and II: GCA GCG GAT CCT CAC TGC ACA GCT TGT TCA T (SEQ ID NO:34) containing DNA sequences encoding the rat Elongin B amino terminus and carboxyl terminus, respectively, were used in PCR reactions to isolate a human Elongin B cDNA from a λZAPII human peripheral blood lymphocyte cDNA library, which was obtained from J. Culpepper and F. Lee (DNAX Research Institute, Palo Alto, CA) . PCR reactions were performed for 30 cycles of 1 min at 94°C, 1 min at 46°C, and 2 min at 72°C with 1.5 mM MgCl 2 , 0.25 mM dATP, 0.25 mM dCTP, 0.25 mM dGTP, 0.25 mM dTTP, 2.5 units of Taq polymerase, 0.02 A260 units of each primer and -4 x IO 6 pfu of the library. PCR products containing Elongin B inserts were identified by Southern blot hybridization using as probe 5'-α- 32 P labelled oligonucleotide III, which encodes residues 81-87 of the rat Elongin B subunit. Appropriately sized PCR products were purified by polyacrylamide gel electrophoresis, and subcloned by blunt-end ligation into pBluescript KS(-). Bacteria harboring a recombinant plasmid carrying the human Elongin B cDNA were identified by colony hybridization using oligonucleotide III: GCN GA(C/T) GA(C/T) ACN TT(C/T) GA(G/A) GC (SEQ ID NO:35) as probe. The resulting cloned PCR product was sequenced by the dideoxy chain termination method using a Sequenase kit. The human Elongin B cDNA encodes a protein with a amino acid sequence that is almost identical to that of rat Elongin B. The human Elongin B nucleotide sequence is given in SEQ ID NO:9 and the corresponding amino acid sequence is listed in SEQ ID NO:10. These findings indicate that the human Elongin B mRNA is expressed in peripheral blood lymphocytes. Tsolation of a cDNA encoding the human Elongin A cDNAs encoding Elongin A were obtained by screening 1 x IO 5 colonies of a pSPORT-1 human umbilical vein endothelial cell (HUVEC) cDNA library with a 32 P-labelled probe comprised of the entire rat Elongin A coding sequence. The library was a gift of Kenji Fukudome (Oklahoma Medical Research Foundation) . Prehybridization was carried out for 2 hrs at 42 °C in 4x SSC, 0. 1 % SDS, 40% formamide, 20 mM Tris-HCI (pH 7.5), 4% dextran sulfate, lx Denhardt's solution, 100 μg/ml salmon sperm DNA. Hybridization was carried out for 16 hr at 42 °C in the above buffer containing radiolabelled probe. Colony lifts were washed twice for 15 min at 42 °C in 2x SSC containing 0.1% SDS. Positive bacterial colonies were purified by two additional rounds of screening under the same conditions except that hybridization was carried out at 45°C, and the two washes were performed at 45 °C for 20 min each. A positive clone (HUVEC-pllO-8) containing the largest insert was sequenced and found to contain all but the 5' end of the human Elongin A. To obtain the 5' end of the human Elongin A cDNA, an aliquot of human liver 5'-RACEReady cDNA (obtained from CLONTECH) was used as a template in PCR reactions. The primary PCR reaction was carried out with the Anchor primer provided by the manufacturer and a primer designated ELA1 (5 1 -GCTTTCTCCCTTGCATTGTCCC-3' ) (SEQ ID NO:36) , which contains a sequence located near the 5' end of the HUVEC-pllO-8 cDNA. A small dilution of the primary PCR reaction products was then used in a secondary PCR reaction with the Anchor primer and the nested primer ELA2 (5'-CCTCTAGAATTTCTCTCTGCTCACCACAGG-3' ) (SEQ ID NO:37) , which contains a sequence located closer to the 5* end of the HUVEC-pllO-8 cDNA than ELA1. The product of the second PCR reaction was gel-purified and subcloned into pUC-18. The clone with the largest insert (Liver-pll0-4) was sequenced. Liver-pll0-4 precisely overlapped the 5' end of HUVEC-pllO-8 and extended further 5' by 818 bp. The predicted open reading frame of the human Elongin A cDNA encodes a 772 amino acid protein, which is 84% identical to rat pllO. EXAMPLE 6 Expression of human Elongin A in E. coli and assay of recombinant human Elongin A transcriptional activity The expression vector pET 16b-hpll0 was constructed by inserting a PCR generated fragment containing the complete human Elongin A open reading frame into the Nde I and Bam HI sites of pET16b (Novagen) . E. coli strain BL2KDE3) transformed with pET16b-hpllO was grown in LB medium containing 50 14g/ml ampicillin at 370C The culture was induced by addition of 1 mM IPTG when it reached an optical density at 600 nn (OD 600 ) of 0.6. After 2.5 hr, cells were harvested by centrifugation at 2000 x g for 10 min at 4°C Inclusion bodies were prepared essentially as described (Lin, K. and Cheng, S. (1991) BioTechniques 11, 748-753) , except that DNAase and RNAase treatments were omitted. Inclusion bodies were solubilized by resuspension in 5 ml of ice cold 50 mM Tris-HCl (pH 8.0) containing 6 M guanidine hydrocholoride. The resulting suspension was clarified by centrifugation at 50,000 x g for 20 min at 4°C Histidine-tagged human Elongin A was purified from the supernatant by affinity chromatography on ProBond metal binding resin (Invitrogen) according to the manufacturer's instructions. The ability of recombinant human Elongin A to support SIII transcription activity when renatured with recombinant Elongin C and Elongin B was tested by the same procedures used to analyze the transcription activity of recombinant rat Elongin A. Recombinant human Elongin A is transcriptionally active. Although Elongin A contains no structural motifs characteristic of transcription factors, such as zinc finger, leucine zipper, or helix-turn-helix domains, a homology search of the GenBank data base revealed that the N-terminus of Elongin A shares significant sequence similarity with the N-terminus of RNA polymerase II elongation factor SII. The two proteins are 29% identical over a 108-amino acid overlap; when conservative amino acid substitutions are included, the sequence similarity is 53%, suggesting that SII and Elongin A are members of a family of related transcription factors. SII N-terminal sequences similar to Elongin A include a phosphorylation domain proposed to regulate SII activity in vivo; this SII region, however, is dispensable for SII transcriptional activity in vitro. By analyzing a series of N- and C-terminal Elongin A deletion mutants, we observed that Elongin A transcriptional activity resides in a 280 amino acid region that includes residues between 400 and 680. Interestingly, within this essential region (between amino acids 530 and 548) is a near-consensus eukaryotic DNA topoisomerase I active site which includes a tyrosine residue at position 543 in rat and position 544 in human Elongin A. The tyrosine residue within this motif is expected to be critical for topoisomerase activity; however, mutation of this residue has no effect on Elongin A transcriptional activity in vitro. EXAMPLE 7 Elongin Effect on Transcription Rate Unlabelled ultrapure ribonucleoside 5*-triphosphates and dATP were from Pharmacia LKB Biotechnology, Inc. AMP-PNP was obtained from Sigma or Pharmacia. [ - 32 P] CTP (>650 Ci/mmol) and [α- 32 P] UTP (>650 Ci/mmol) were obtained from ICN. Sarkosyl and heparin were from Sigma. Bovine serum albumin (Pentex fraction V) was obtained from ICN Immunobiologicals. Agarose (GenAR) was from Mallinckrodt (St. Louis, MO) . Preparation of RNA polymerase TT and transcription factors Elongin was purified from rat liver nuclear extracts as described in Example 1. Recombinant yeast TFIID was expressed and purified as described (Conaway, et al., J Biol Chem 266: 7804-7811 (1991)) from bacterial strain N5151 containing the plasmid pASY2FD (Schmidt, et al., Proc Natl Acad Sci USA 86: 7785-7789 (1989)). Recombinant rat TFIID was expressed in Escherichia coli using T7-expression vector pET-lla (Novagen) and was purified from extracts by chromatography on DEAE Sepharose and heparin Sepharose as described (Hoey, et al., Cell 61: 1179-1186 (1990)). Recombinant rat (TFIIB) (Tsuboi, et al., Nucleic Acids Res 20: 3250 (1992)) and recombinant human TFIIE (Peterson, et al., Nature 354: 369-373 (1991)) were prepared as described, except that the 56 kDa subunit of TFIIE was expressed in BL2KDE3). Recombinant βγ(TFIIF) was purified by phosphocellulose chromatography (Conaway, J.W. and Conaway, R.C, J Biol Chem 264: 2357-2362 (1989)), of whole cell extracts prepared from Sf21 cells co-infected with recombinant baculoviruses encoding human RAP74 (Aso, et al., Nature 355: 461-464 (1992); Finkelstein, et al., Nature 355: 464-467 (1992)) and rat RAP30 (Garrett, et al., J Biol Chem 267: 23942-23949 (1992)). Recombinant viruses were constructed using the BacPAK6 baculovirus expression system (Clontech) . RΝA polymerase II (Serizawa, et al., Proc Natl Acad Sci USA 89: 7476-7480 (1992)), the native rat TATA factor τ (Conaway, et al., J Biol Chem 265: 7552-7558 (1990)), and transcription factor δ(BTF2) (Conaway, R.C and Conaway, J.W. , Proc Natl Acad Sci USA 86: 7356-7360 (1989)); Conaway, et al., J Biol Chem 267: 10142-10148) (1992)) were purified from rat liver as previously described. Assay of runoff transcription Unless indicated otherwise, preinitiation complexes were assembled as described (Conaway, et al., J Biol Chem 262: 8293-8297 (1987)) by preincubation of 100 ng of Νde I-digested pDN-AdML (Conaway, R.C. and Conaway, J.W. , J Biol Chem 263: 2962-2968 (1988)), 100 ng of Nde I- digested pN 4 (Lorch, et al., Cell 49: 203-210 (1987)), or 10 ng of the Eeo RI to Nde I fragment from pDN-AdML, and approximately 10 ng of recombinant α(TFIIB), 10 ng of recombinant βγ(TFIIF), 7 ng of recombinant human TFIIE, 40 ng of δ(BTF2) (Fraction VI), 60 ng τ (Fraction V) or 50 ng of recombinant yeast TFIID (AcA 44 fraction) , and 0.01 unit of RNA polymerase II. Transcription was initiated by addition of 7 mM MgCl 2 and ribonucleoside triphosphates in the concentrations noted below. After incubation at 28°C, runoff transcripts were analyzed by electrophoresis through 6% polyacrylamide/7.0 M urea gels. Transcription was quantitated by densitometry of autoradiograms using an LKB UltroScan XL laser densitometer. Tsola ion of DNA fragments DNA fragments were excised from 1.5% agarose gels and purified using GENECLEAN II (BIO 101 Inc.) according to the manufacturer's instructions. Determination of Transcription Rate AMP-PNP is used less well than ATP as a substrate for RNA chain elongation (Ernst, et al., Mol Cell Biol 3: 2172-2179 (1983)). At AMP-PNP concentrations <10 μM, full length runoff transcripts initiated from the AdML promoter do not accumulate, but there is a substantial accumulation of shorter products. At AMP-PNP concentrations >10 μM, significant synthesis of full length runoff transcripts is observed. Furthermore, the short RNA products formed in the presence of low concentrations of AMP-PNP can be chased into full length runoff transcripts if ATP is added to reaction mixtures after the addition of heparin, which inhibits promoter- specific transcription initiation but not elongation of previously initiated RNA chains (Conaway, R.C. and Conaway, J.W., J Biol Chem 265: 7559-7563 (1990); Egly, et al., EMBO J 3: 2363-2371 (1984)). Regardless of the AMP-PNP concentration present in reaction mixtures prior to the ATP chase, roughly equivalent levels of runoff transcripts were synthesized from the AdML promoter following addition of heparin and ATP. Thus, the short transcripts formed in the presence of low AMP-PNP concentrations and in the absence of Elongin are not terminated, but, rather, appear to be contained in transcriptionally active but stalled RNA polymerase II elongation complexes. To determine whether the effect of Elongin is a general or whether it is specific for reactions in which AMP-PNP replaces ATP as a substrate for RNA chain elongation, runoff transcription assays were performed, with and without Elongin, in which the concentration of each of the four ribonucleoside triphosphates was lowered individually in the presence of fixed concentrations of the other three ribonucleoside triphosphates. Elongin is able to stimulate synthesis of accurately initiated transcripts when reactions are carried out with limiting concentrations of any of the ribonucleoside triphosphates. During a 30 min incubation, maximal stimulation of transcription was observed when the limiting ribonucleoside triphosphate was included in reaction mixtures at concentrations less than 2 μM. The extent to which Elongin stimulates accumulation of full length products appears to differ depending on which ribonucleoside triphosphate is limiting. Examination of the kinetics of accumulation of full- length runoff transcripts revealed that Elongin significantly increases the rate of incorporation of ribonucleoside triphosphates into growing RNA chains. (See Fig. 2) An investigation of the effect of Elongin on runoff transcription was also carried out in the presence of limiting UTP. Under these conditions, full- length runoff transcripts synthesized in the absence of Elongin were first detected approximately 24 min after addition of ribonucleoside triphosphates. In contrast, full-length runoff transcripts synthesized in the presence of Elongin were detected within 4 min after addition of ribonucleoside triphosphates. Transcriptional stimulation by Elongin is not limited to cases in which one or more of the ribonucleoside triphosphates are present in reaction mixtures at very low concentrations. Analysis of the effect of Elongin on transcription at very early times after initiation indicates that the factor also increases the rate of accumulation of full-length runoff transcripts synthesized in the presence of ribonucleoside triphosphates at the concentrations (50 μM ATP, 50 μM UTP, 50 μM GTP, and 10 μM CTP) normally used in our standard transcription assays. Under these conditions, full-length runoff transcripts synthesized in the absence of Elongin were first detected -6 min after addition of ribonucleoside triphosphates. In contrast, full-length runoff transcripts synthesized in the presence of Elongin could be detected within 1 min after addition of ribonucleoside triphosphates. Thus, Elongin stimulates the rate of RNA chain elongation at least five-fold when transcription is carried out both at very low ribonucleoside triphosphate concentrations and at ribonucleoside triphosphate concentrations used in our standard runoff transcription assays. In addition, we observed that Elongin is able to stimulate the rate of RNA chain elongation to a similar extent when all nucleotides are at a concentration of 500 μM. Although there is synthesis of multiple short transcripts when transcription is carried out in the presence of limiting AMP-PNP or UTP, most of these transcripts can be chased into full-length runoff transcripts either by increasing the concentration of the limiting nucleotide or by addition of Elongin indicating that RNA polymerase II pauses at multiple sites during synthesis of transcripts initiated from the AdML promoter on pDN-AdML, (Conaway, R.C and Conaway, J.W., J Biol Chem 263: 2962-2968 (1988)). To determine whether RNA polymerase II pauses at these sites simply as a consequence of limiting levels of ribonucleoside triphosphates or whether polymerase pauses in response to specific DNA sequences that promote pausing regardless of ribonucleoside triphosphate concentration, we compared the lengths of short transcripts synthesized in the presence of low concentrations of each of the four ribonucleoside triphosphates. Distinct sets of RNA products are synthesized in the presence of low concentrations of UTP, ATP, GTP, and CTP, suggesting that most of the RNA polymerase II elongation complexes are not pausing at DNA-sequences that function as specific pause signals. Instead, pause sites appear to be specific for and induced by the limiting ribonucleoside triphosphate. It is noteworthy that, although the 3' termini of RNA in paused elongation complexes have not been established unequivocally, most of them map roughly to DNA sequences encoding two or more sequential residues of the limiting nucleotide (data not shown) . Like Elongin, the general initiation factor βγ(TFIIF) has been shown previously to stimulate the rate of RNA chain elongation by RNA polymerase II (Price, et al., Mol Cell Biol 9: 1465-1475 (1989); Flores, et al., J Biol Chem 264: 8913-8921 (1989); Bengal, et al. , Mol Cell Biol 11: 1195-1206 (1991); Kato, et al. , Genes Dev 6: 655-666 (1992); and Izban, M.G. and Luse, D.S., J Biol Chem 267: 13647-13655 (1992)). The ability of the two factors to stimulate transcription initiated at the oligo-dC tail of pCpGR220 S/P/X or at the AdML promoter was compared. The recombinant βy(TFIIF) used in these experiments was expressed in and purified from insect cells and was more than 95% pure. In another procedure, transcription was initiated by addition of purified RNA polymerase II to reaction mixtures containing pCpGR220 S/P/X and 50 μM ATP, 50 μM GTP, and 2 μM [ 32 -P]CTP. After a 30 min incubation to allow synthesis of short, labelled transcripts, the accumulated transcripts were chased with 500 μM non¬ radioactive CTP, ATP, GTP, and UTP, in the presence or absence of Elongin or βγ(TFIIF) . Under these conditions, both βγ(TFIIF) and Elongin strongly stimulate the rate of RNA chain elongation. We estimate that transcription elongation in the presence of either factor is approximately 500 nucleotides/minute. Preinitiation complexes were assembled at the AdML promoter by preincubation of template DNA with RNA polymerase II and initiation factors; reactions contained an amount of βγ(TFIIF) just sufficient to produce maximal levels of initiation. Transcription was then initiated by addition of ATP, GTP, and a low concentration of UTP and [ 32 -P]CTP. After a 12 min incubation to allow synthesis of short labelled transcripts, the radioactive CTP was diluted by addition of an approximately 30-fold excess of non-radioactive CTP, and varying amounts of Elongin or additional βγ(TFIIF) were added to reactions. Under some of these conditions, Elongin strongly stimulates accumulation of full length runoff transcripts from the AdML promoter. Likewise, addition of βγ(TFIIF), in quantities greater than that sufficient to saturate the reaction for initiation, stimulates accumulation of full length runoff transcripts. SEQUENCE LISTING (1) GENERAL INFORMATION : (i) APPLICANT: (A) NAME: Oklahoma Medical Research Foundation (B) STREET: 825 NE 13th Street (C) CITY: Oklahoma City (D) STATE: Oklahoma (E) COUNTRY: US (F) POSTAL CODE (ZIP) : 73104 (G) TELEPHONE: 405-271-7660 (H) TELEFAX: 405-271-3153 (ii) TITLE OF INVENTION: RNA Polymerase Transcription Factor (iii) NUMBER OF SEQUENCES: 37 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: SIDLEY & AUSTIN (B) STREET: 1201 Elm Street, Suite 4500 (C) CITY: Dallas (D) STATE: TX (E) COUNTRY: US (F) ZIP: 75270-2197 (v) COMPUTER READABLE FORM: (A) MEDIUM TYPE: Floppy disk (B) COMPUTER: IBM PC compatible (C) OPERATING SYSTEM: PC-DOS/MS-DOS (D) SOFTWARE: Patentin Release #1.0, Version #1.30 (vi) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: (C) CLASSIFICATION: (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: US 08/524757 (B) FILING DATE: 07-SEP-1995 (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: PCT/US94/13621 (B) FILING DATE: 29-NOV-1994 (vii) PRIOR APPLICATION DATA: (A) APPLICATION NUMBER: US 08/160087 (B) FILING DATE: 30-NOV-1993 (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Harre, John A. (B) REGISTRATION NUMBER: 37,345 (C) REFERENCE/DOCKET NUMBER: 11146/06508 (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (214) 981-3300 (B) TELEFAX: (214) 981-3400 (2) INFORMATION FOR SEQ ID NO:l: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 458 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 46..381 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:l: ACTAGTAACT TCCTCTGGGA TCAAATAGAA TTTTATAAGA ACACA ATG GAT GGA 54 Met Asp Gly 1 GAG GAG AAA ACC TAT GGT GGC TGT GAA GGC CCT GAT GCC ATG TAT GTG 102 Glu Glu Lys Thr Tyr Gly Gly Cys Glu Gly Pro Asp Ala Met Tyr Val 5 10 15 AAA TTA ATA TCT TCT GAT GGT CAT GAA TTT ATT GTA AAA AGA GAA CAT 150 Lys Leu lie Ser Ser Asp Gly His Glu Phe lie Val Lys Arg Glu His 20 25 30 35 GCA TTA ACA TCA GGA ACA ATA AAG GCC ATG TTG AGT GGT CCA GGT CAG 198 Ala Leu Thr Ser Gly Thr lie Lys Ala Met Leu Ser Gly Pro Gly Gin 40 45 50 TTT GCG GAG AAT GAA ACC AAT GAG GTC AAC TTT AGA GAG ATC CCT TCA 246 Phe Ala Glu Asn Glu Thr Asn Glu Val Asn Phe Arg Glu lie Pro Ser 55 60 65 CAT GTG CTA TCG AAA GTG TGC ATG TAT TTT ACC TAC AAG GTC CGC TAT 294 His Val Leu Ser Lys Val Cys Met Tyr Phe Thr Tyr Lys Val Arg Tyr 70 75 80 ACT AAC AGC TCC ACT GAA ATT CCT GAA TTC CCA ATT GCA CCT GAA ATT 342 Thr Asn Ser Ser Thr Glu lie Pro Glu Phe Pro lie Ala Pro Glu lie 85 90 95 GCA CTG GAA CTG CTG ATG GCC GCG AAC TTC CTA GAT TGT TAAATAAAAT 391 Ala Leu Glu Leu Leu Met Ala Ala Asn Phe Leu Asp Cys 100 105 110 AAATTATAAT AAACTGTTAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA 451 AAAAAAA 458 (2) INFORMATION FOR SEQ ID NO:2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 112 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:2: Met Asp Gly Glu Glu Lys Thr Tyr Gly Gly Cys Glu Gly Pro Asp Ala 1 5 10 15 Met Tyr Val Lys Leu lie Ser Ser Asp Gly His Glu Phe lie Val Lys 20 25 30 Arg Glu His Ala Leu Thr Ser Gly Thr lie Lys Ala Met Leu Ser Gly 35 40 45 Pro Gly Gin Phe Ala Glu Asn Glu Thr Asn Glu Val Asn Phe Arg Glu 50 55 60 lie Pro Ser His Val Leu Ser Lys Val Cys Met Tyr Phe Thr Tyr Lys 65 70 75 80 Val Arg Tyr Thr Asn Ser Ser Thr Glu lie Pro Glu Phe Pro lie Ala 85 90 95 Pro Glu lie Ala Leu Glu Leu Leu Met Ala Ala Asn Phe Leu Asp Cys 100 105 110 (2) INFORMATION FOR SEQ ID NO:3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 354 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..354 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:3: ATG GAC GTG TTT CTC ATG ATC CGG CGC CAC AAG ACC ACC ATC TTT ACG 48 Met Asp Val Phe Leu Met lie Arg Arg His Lys Thr Thr lie Phe Thr 1 5 10 15 GAC GCC AAG GAG TCG AGC ACG GTG TTC GAA CTG AAG CGC ATC GTC GAG 96 Asp Ala Lys Glu Ser Ser Thr Val Phe Glu Leu Lys Arg lie Val Glu 20 25 30 GGC ATC CTC AAG CGG CCG CCA GAG GAG CAG CGG CTG TAC AAG GAC GAC 144 Gly lie Leu Lys Arg Pro Pro Glu Glu Gin Arg Leu Tyr Lys Asp Asp 35 40 45 CAG CTC CTT GAT GAT GGA AAA ACT CTG GGC GAA TGT GGC TTC ACC AGT 192 Gin Leu Leu Asp Asp Gly Lys Thr Leu Gly Glu Cys Gly Phe Thr Ser 50 55 60 CAG ACA GCA AGG CCA CAG GCC CCA GCC ACA GTG GGC CTG GCC TTT CGA 240 Gin Thr Ala Arg Pro Gin Ala Pro Ala Thr Val Gly Leu Ala Phe Arg 65 70 75 80 GCA GAT GAC ACC TTT GAA GCG CTG CGT ATT GAA CCC TTC TCC AGC CCT 288 Ala Asp Asp Thr Phe Glu Ala Leu Arg lie Glu Pro Phe Ser Ser Pro 85 90 95 CCG GAG CTT CCA GAT GTG ATG AAG CCA CAG GAT TCT GGA GGC AGT GCC 336 Pro Glu Leu Pro Asp Val Met Lys Pro Gin Asp Ser Gly Gly Ser Ala 100 105 110 AAT GAA CAA GCT GTG CAG 354 Asn Glu Gin Ala Val Gin 115 (2) INFORMATION FOR SEQ ID NO:4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 118 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:4: Met Asp Val Phe Leu Met lie Arg Arg His Lys Thr Thr lie Phe Thr 1 5 10 15 Asp Ala Lys Glu Ser Ser Thr Val Phe Glu Leu Lys Arg lie Val Glu 20 25 30 Gly lie Leu Lys Arg Pro Pro Glu Glu Gin Arg Leu Tyr Lys Asp Asp 35 40 45 Gin Leu Leu Asp Asp Gly Lys Thr Leu Gly Glu Cys Gly Phe Thr Ser 50 55 60 Gin Thr Ala Arg Pro Gin Ala Pro Ala Thr Val Gly Leu Ala Phe Arg 65 70 75 80 Ala Asp Asp Thr Phe Glu Ala Leu Arg lie Glu Pro Phe Ser Ser Pro 85 90 95 Pro Glu Leu Pro Asp Val Met Lys Pro Gin Asp Ser Gly Gly Ser Ala 100 105 110 Asn Glu Gin Ala Val Gin 115 (2) INFORMATION FOR SEQ ID NO:5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 3501 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 82..2403 (ix) FEATURE: (A) NAME/KEY: misc_difference (B) LOCATION: replace(2990, "") (D) OTHER INFORMATION: /note= "This base can be either a, c, t, g." (xi) SEQUENCE DESCRIPTION: SEQ ID NO:5: CGTTGCTGTC GAGGGCGGAG TTGCGGCCCG AGGACGCTAC GCGAGCCCAG TTCCGGCGAG 60 GAGGCCGCGC CAGTGACAGC G ATG GCG GCG GAG TCG GCG CTC CAA GTT GTG 111 Met Ala Ala Glu Ser Ala Leu Gin Val Val 1 5 10 GAG AAG CTG CAG GCG CGC CTG GCT GCG AAC CCG GAC CCC AAG AAG CTA 159 Glu Lys Leu Gin Ala Arg Leu Ala Ala Asn Pro Asp Pro Lys Lys Leu 15 20 25 TTG AAA TAT TTG AAG AAA CTT TCC GTC TTA CCT ATT ACA GTA GAC ATT 207 Leu Lys Tyr Leu Lys Lys Leu Ser Val Leu Pro lie Thr Val Asp lie 30 35 40 CTT GTG GAG ACT GGG GTG GGG AAA ACA GTG AAC AGC TTT CGG AAA CAT 255 Leu Val Glu Thr Gly Val Gly Lys Thr Val Asn Ser Phe Arg Lys His 45 50 55 GAG CAA GTG GGA AAC TTT GCC AGA GAC CTG GTT GCC CAG TGG AAG AAG 303 Glu Gin Val Gly Asn Phe Ala Arg Asp Leu Val Ala Gin Trp Lys Lys 60 65 70 CTG GTT CCA GTA GAA CGA AAC AAT GAG GCT GAG GAT CAG GAT TTT GAG 351 Leu Val Pro Val Glu Arg Asn Asn Glu Ala Glu Asp Gin Asp Phe Glu 75 80 85 90 AAG AGC AAT TCC CGC AAG CGT CCC CGA GAT GTT CCC CAG CAG GAG GAG 399 Lys Ser Asn Ser Arg Lys Arg Pro Arg Asp Val Pro Gin Gin Glu Glu 95 100 105 GAA GCG GAG GGG AAC TAC CAG GAA AGC TGG CAA GCC TCA GGC AGC CAG 447 Glu Ala Glu Gly Asn Tyr Gin Glu Ser Trp Gin Ala Ser Gly Ser Gin 110 115 120 CCC TAC AGC CCT GAG CAC AGA CAG AAA AAG CAC AGA AAA CTT CCT GAG 495 Pro Tyr Ser Pro Glu His Arg Gin Lys Lys His Arg Lys Leu Pro Glu 125 130 135 CTT GAA AGG CCT CAC AAA GTG GCT CAT GGT CAC GAG AGG AGA GAT GAA 543 Leu Glu Arg Pro His Lys Val Ala His Gly His Glu Arg Arg Asp Glu 140 145 150 AGG AAG AGG TGT CAC AAA GTG TCA CCA CCA TAT TCT TCA GAC CCC GAG 591 Arg Lys Arg Cys His Lys Val Ser Pro Pro Tyr Ser Ser Asp Pro Glu 155 160 165 170 TCG TCT GAC TAT GGT CAT GTT CAA TCT CCT CCA CCT TCA AGT CCC CAT 639 Ser Ser Asp Tyr Gly His Val Gin Ser Pro Pro Pro Ser Ser Pro His 175 180 185 CAA ATG TAT ACA GAC CTC TCT AGG TCC CCA GAG ATG GAC CAG GAA CCC 687 Gin Met Tyr Thr Asp Leu Ser Arg Ser Pro Glu Met Asp Gin Glu Pro 190 195 200 ATC GTC TCA CAC CCG AAG CCT GGG AAA GTC CAC AGT AAT ACC TTT CAG 735 lie Val Ser His Pro Lys Pro Gly Lys Val His Ser Asn Thr Phe Gin 205 210 215 GAC AGA CTA GGG GTT AGT CAC CTG GGT GAG CAC CAA GGG AAA GGG GCT 783 Asp Arg Leu Gly Val Ser His Leu Gly Glu His Gin Gly Lys Gly Ala 220 225 230 GTT AGC CAA AAC AAG CCA CAC AAA TCT TCC CAC AAG GAG AAA CGC CCT 831 Val Ser Gin Asn Lys Pro His Lys Ser Ser His Lys Glu Lys Arg Pro 235 240 245 250 GTG GAT GCC AGG GGG GAT GAG AAG AGC TCT GTC ATG GGC AGA GAG AAG 879 Val Asp Ala Arg Gly Asp Glu Lys Ser Ser Val Met Gly Arg Glu Lys 255 260 265 TCA CAC AAA GCC TCT TCC AAA GAG GAG AGC CGA AGG CTA CTC TCA GAG 927 Ser His Lys Ala Ser Ser Lys Glu Glu Ser Arg Arg Leu Leu Ser Glu 270 275 280 GAC AGT GCC AAG GAG AAG CTG CCC TCC AGT GTT GTC AAG AAA GAG AAG 975 Asp Ser Ala Lys Glu Lys Leu Pro Ser Ser Val Val Lys Lys Glu Lys 285 290 295 GAC AGA GAA GGC AAC AGC CTC AAG AAG AAG TTG TCA CCT GCC TTA GAT 1023 Asp Arg Glu Gly Asn Ser Leu Lys Lys Lys Leu Ser Pro Ala Leu Asp 300 305 310 GTT GCT TCA GAC AAC CAC TTT AAA AAG CCC AAA CAC AAG GAC TCC GAG 1071 Val Ala Ser Asp Asn His Phe Lys Lys Pro Lys His Lys Asp Ser Glu 315 320 325 330 AAA ATC AAG TCT GAC AAA AAC AAG CAG AGT GTA GAT AGC GTG GAC TCA 1119 Lys He Lys Ser Asp Lys Asn Lys Gin Ser Val Asp Ser Val Asp Ser 335 340 345 GGA CGA GGG ACA GGA GAC CCA TTA CCC AGA GCC AAG GAT AAA GTT CCC 1167 Gly Arg Gly Thr Gly Asp Pro Leu Pro Arg Ala Lys Asp Lys Val Pro 350 355 360 AAC AAC CTG AAG GCT CAG GAG GGG AAA GTA AGA ACT AAC TCG GAT CGA 1215 Asn Asn Leu Lys Ala Gin Glu Gly Lys Val Arg Thr Asn Ser Asp Arg 365 370 375 AAG TCA CCA GGC TCA CTC CCT AAA GTA GAA GAG ATG GAC ATG GAT GAT 1263 Lys Ser Pro Gly Ser Leu Pro Lys Val Glu Glu Met Asp Met Asp Asp 380 385 390 GAG TTT GAG CAG CCC ACC ATG TCC TTT GAG TCA TAC CTC AGC TAT GAC 1311 Glu Phe Glu Gin Pro Thr Met Ser Phe Glu Ser Tyr Leu Ser Tyr Asp 395 400 405 410 CAG CCC CGC AAG AAA AAG AAG AAG GTT GTG AAA ACT TCC GGT ACA GCA 1359 Gin Pro Arg Lys Lys Lys Lys Lys Val Val Lys Thr Ser Gly Thr Ala 415 420 425 CTT GGA GAA AAA GGA CTT AAA AAG AAG GAC TCT AAA AGC ACT AGT AAA 1407 Leu Gly Glu Lys Gly Leu Lys Lys Lys Asp Ser Lys Ser Thr Ser Lys 430 435 440 AAC TTG AAC TCG GCT CAG AAA TTA CCC AAG GCG AAT GAA AAC AAG TCA 1455 Asn Leu Asn Ser Ala Gin Lys Leu Pro Lys Ala Asn Glu Asn Lys Ser 445 450 455 GAC AAG TTG CAG CCA GCT GGA GCC GAA CCC ACG AGG CCT AGA AAG GTC 1503 Asp Lys Leu Gin Pro Ala Gly Ala Glu Pro Thr Arg Pro Arg Lys Val 460 465 470 CCT ACT GAT GTG CTG CCA GCA TTG CCA GAC ATC CCC TTG CCC GCC ATA 1551 Pro Thr Asp Val Leu Pro Ala Leu Pro Asp He Pro Leu Pro Ala He 475 480 485 490 CAA ACC AAC TAT CGT CCC CTT CCC TCC CTC GAG TTG ATC TCC TCC TTT 1599 Gin Thr Asn Tyr Arg Pro Leu Pro Ser Leu Glu Leu He Ser Ser Phe 495 500 505 CAG CCA AAG CGA AAA GCT TTC TCT TCA CCC CAG GAA GAA GAA GAA GCT 1647 Gin Pro Lys Arg Lys Ala Phe Ser Ser Pro Gin Glu Glu Glu Glu Ala 510 515 520 GGG TTC ACA GGA CGC AGA ATG AAT TCT AAG ATG CAG GTG TAT TCA GGT 1695 Gly Phe Thr Gly Arg Arg Met Asn Ser Lys Met Gin Val Tyr Ser Gly 525 530 535 TCC AAG TGT GCC TAT CTC CCC AAA ATG ATG ACC TTG CAC CAG CAG TGT 1743 Ser Lys Cys Ala Tyr Leu Pro Lys Met Met Thr Leu His Gin Gin Cys 540 545 550 ATC CGG GTG CTT AAG AAT AAT ATT GAC TCC ATC TTT GAA GTG GGA GGA 1791 He Arg Val Leu Lys Asn Asn He Asp Ser He Phe Glu Val Gly Gly 555 560 565 570 GTC CCC TAT TCT GTT CTT GAA CCT GTC TTG GAG AGG TGC ACA CCC GAT 1839 Val Pro Tyr Ser Val Leu Glu Pro Val Leu Glu Arg Cys Thr Pro Asp 575 580 585 CAG CTC TAC CGA ATA GAG GAA TGC AAT CAT GTA TTA ATT GAG GAA ACA 1887 Gin Leu Tyr Arg He Glu Glu Cys Asn His Val Leu He Glu Glu Thr 590 595 600 GAT CAG TTG TGG AAA GTT CAC TGT CAC CGG GAC TTT AAG GAA GAA AGA 1935 Asp Gin Leu Trp Lys Val His Cys His Arg Asp Phe Lys Glu Glu Arg 605 610 615 CCA GAA GAG TAT GAG TCT TGG AGG GAG ATG TAC CTG AGG CTT CAG GAC 1983 Pro Glu Glu Tyr Glu Ser Trp Arg Glu Met Tyr Leu Arg Leu Gin Asp 620 625 630 GCC CGA GAG CAG CGG CTG CGC CTG CTC ACA AAC AAC ATC CGG TCT GCA 2031 Ala Arg Glu Gin Arg Leu Arg Leu Leu Thr Asn Asn He Arg Ser Ala 635 640 645 650 CAT GCC AAT AAG CCA AAA GGA CGA CAA GCA AAG ATG GCC TTT GTG AAC 2079 His Ala Asn Lys Pro Lys Gly Arg Gin Ala Lys Met Ala Phe Val Asn 655 660 665 TCT GTG GCC AAG CCA CCG AGA GAT GTT CGA CGG AGG CAG GAG AAG TTT 2127 Ser Val Ala Lys Pro Pro Arg Asp Val Arg Arg Arg Gin Glu Lys Phe 670 675 680 GGA ACC GGG GGA GCA GCT GTC CCT GAG AAA GTC AGG ATT AAG CCA GCA 2175 Gly Thr Gly Gly Ala Ala Val Pro Glu Lys Val Arg He Lys Pro Ala 685 690 695 CCA TAT ACA ACA GGA AGC AGC CAT GTT CCT GCC AGC AAC AGC AGC AGC 2223 Pro Tyr Thr Thr Gly Ser Ser His Val Pro Ala Ser Asn Ser Ser Ser 700 705 710 AGC TTC CAC TCA AGT CCT GAG GAG CTG GCC TAC GAA GGG CCC AGT ACC 2271 Ser Phe His Ser Ser Pro Glu Glu Leu Ala Tyr Glu Gly Pro Ser Thr 715 720 725 730 AGC AGT GCC CAC TTA GCT CCT GTG GCC AGC AGC TCT GTT TCC TAT GAT 2319 Ser Ser Ala His Leu Ala Pro Val Ala Ser Ser Ser Val Ser Tyr Asp 735 740 745 CCC AGG AAA CCA GCT GTG AAG AAA ATT GCC CCG ATG ATG GCC AAG ACC 2367 Pro Arg Lys Pro Ala Val Lys Lys He Ala Pro Met Met Ala Lys Thr 750 755 760 ATT AAA GCA TTC AAG AAC AGA TTT TCC CGA CGA TAA ACAGGACTTG 2413 He Lys Ala Phe Lys Asn Arg Phe Ser Arg Arg * 765 770 CCTTGGAGGT TGAGTCTGGA AGCAGGACTA CAGGGACTAT GGGGACGGGA GAAGAGGATG 2473 TCCACAGAAG ACCCGTATCT TTTGCTCTGT GGAACTTTTG GCCTCTGACT CCTGCACAGT 2533 TCCAGGTGTC CCCCTCTGTG CCTCAGCCCT GCACCCTGCT TGTAGCACAC TAGTTTTAAT 2593 TAATAAATAT TGCCCCCAGA TGTATTTATA ATACCCCAGG GGTTTTTATT TTATTTTATT 2653 TTCTCTTTGG TCCACTATAT TTAGCCTTCA GATTTCTGAA GACAGTATGA GCCTCAGTCT 2713 TACTGAGGAC TTTAAGATCA GTTATACTTT TGTTGCTAAT TAGCATCTTT GTAAACTATA 2773 AGACACTTTA CTTTCCAGGT CCTTTATTAA AGTTAGATGA GCCTAGCGAA AGCCATTCTT 2833 GTCCTAGTCA GCTCTTCTGA GTAGACACTG GTCCTTCAGA GCCAGTGTGT CACTCCAAAC 2893 CCAGATGCAG GGCTAGGAGT GAGTGAGTGC CAGGATGCCT GTCCTCCAGG GGAGCCTCCC 2953 TGCTGAAACC CCCACTGTTC CTTGGTGGGC ACTTTTACTT CAGTAGATTT GTTAAGGAAG 3013 GCCGTTTGCA TCATCTTCAA AGCATACTAC TCTCCCCCAT TTTCCAGCTC ACTGGAGGAC 3073 AGAGCCTAAG AGATGAACTG ATGTAGGACC TCAGCAGTTT TATAATTTTA GTTTCTGGTT 3133 CAGTATTTTA CACACAGACA GACACACAGA CACACAGACC CTTCCTTATT TTGTCTCTCC 3193 CTGCACTGTG GGGAAACACA CATGACAGGG CTTTTGTAGC TCTGATGTGG TTGGGGGGTT 3253 TGAAAAGCCA GCACTTTATT TCCTTGTTCT CTATGAATTC CTACCAGGAG TGAGTGGTTT 3313 AGAGCATTGT AGTGCTGTGA AGCTTGCTCG TGTTGGACAG GAAAGGTGCT GACGTGGCCA 3373 GAGGAGCAGC AGTGCACTGT AGCCAGCAGA GAACTCTGTG AAGCCTCCGC CTTCTGAGTG 3433 TTGGCCAGAG TTAGGGATGG GCCACCTGCC GAAGGGTAGA TGGTCACCCT GGTCCCAGCC 3493 AGTCAGTT 3501 (2) INFORMATION FOR SEQ ID NO:6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 774 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:6: Met Ala Ala Glu Ser Ala Leu Gin Val Val Glu Lys Leu Gin Ala Arg 1 5 10 15 Leu Ala Ala Asn Pro Asp Pro Lys Lys Leu Leu Lys Tyr Leu Lys Lys 20 25 30 Leu Ser Val Leu Pro He Thr Val Asp He Leu Val Glu Thr Gly Val 35 40 45 Gly Lys Thr Val Asn Ser Phe Arg Lys His Glu Gin Val Gly Asn Phe 50 55 60 Ala Arg Asp Leu Val Ala Gin Trp Lys Lys Leu Val Pro Val Glu Arg 65 70 75 80 Asn Asn Glu Ala Glu Asp Gin Asp Phe Glu Lys Ser Asn Ser Arg Lys 85 90 95 Arg Pro Arg Asp Val Pro Gin Gin Glu Glu Glu Ala Glu Gly Asn Tyr 100 105 110 Gin Glu Ser Trp Gin Ala Ser Gly Ser Gin Pro Tyr Ser Pro Glu His 115 120 125 Arg Gin Lys Lys His Arg Lys Leu Pro Glu Leu Glu Arg Pro His Lys 130 135 140 Val Ala His Gly His Glu Arg Arg Asp Glu Arg Lys Arg Cys His Lys 145 150 155 160 Val Ser Pro Pro Tyr Ser Ser Asp Pro Glu Ser Ser Asp Tyr Gly His 165 170 175 Val Gin Ser Pro Pro Pro Ser Ser Pro His Gin Met Tyr Thr Asp Leu 180 185 190 Ser Arg Ser Pro Glu Met Asp Gin Glu Pro He Val Ser His Pro Lys 195 200 205 Pro Gly Lys Val His Ser Asn Thr Phe Gin Asp Arg Leu Gly Val Ser 210 215 220 His Leu Gly Glu His Gin Gly Lys Gly Ala Val Ser Gin Asn Lys Pro 225 230 235 240 His Lys Ser Ser His Lys Glu Lys Arg Pro Val Asp Ala Arg Gly Asp 245 250 255 Glu Lys Ser Ser Val Met Gly Arg Glu Lys Ser His Lys Ala Ser Ser 260 265 270 Lys Glu Glu Ser Arg Arg Leu Leu Ser Glu Asp Ser Ala Lys Glu Lys 275 280 285 Leu Pro Ser Ser Val Val Lys Lys Glu Lys Asp Arg Glu Gly Asn Ser 290 295 300 Leu Lys Lys Lys Leu Ser Pro Ala Leu Asp Val Ala Ser Asp Asn His 305 310 315 320 Phe Lys Lys Pro Lys His Lys Asp Ser Glu Lys He Lys Ser Asp Lys 325 330 335 Asn Lys Gin Ser Val Asp Ser Val Asp Ser Gly Arg Gly Thr Gly Asp 340 345 350 Pro Leu Pro Arg Ala Lys Asp Lys Val Pro Asn Asn Leu Lys Ala Gin 355 360 365 Glu Gly Lys Val Arg Thr Asn Ser Asp Arg Lys Ser Pro Gly Ser Leu 370 375 380 Pro Lys Val Glu Glu Met Asp Met Asp Asp Glu Phe Glu Gin Pro Thr 385 390 395 400 Met Ser Phe Glu Ser Tyr Leu Ser Tyr Asp Gin Pro Arg Lys Lys Lys 405 410 415 Lys Lys Val Val Lys Thr Ser Gly Thr Ala Leu Gly Glu Lys Gly Leu 420 425 430 Lys Lys Lys Asp Ser Lys Ser Thr Ser Lys Asn Leu Asn Ser Ala Gin 435 440 445 Lys Leu Pro Lys Ala Asn Glu Asn Lys Ser Asp Lys Leu Gin Pro Ala 450 455 460 Gly Ala Glu Pro Thr Arg Pro Arg Lys Val Pro Thr Asp Val Leu Pro 465 470 475 480 Ala Leu Pro Asp He Pro Leu Pro Ala He Gin Thr Asn Tyr Arg Pro 485 490 495 Leu Pro Ser Leu Glu Leu He Ser Ser Phe Gin Pro Lys Arg Lys Ala 500 505 510 Phe Ser Ser Pro Gin Glu Glu Glu Glu Ala Gly Phe Thr Gly Arg Arg 515 520 525 Met Asn Ser Lys Met Gin Val Tyr Ser Gly Ser Lys Cys Ala Tyr Leu 530 535 540 Pro Lys Met Met Thr Leu His Gin Gin Cys He Arg Val Leu Lys Asn 545 550 555 560 Asn He Asp Ser He Phe Glu Val Gly Gly Val Pro Tyr Ser Val Leu 565 570 575 Glu Pro Val Leu Glu Arg Cys Thr Pro Asp Gin Leu Tyr Arg He Glu 580 585 590 Glu Cys Asn His Val Leu He Glu Glu Thr Asp Gin Leu Trp Lys Val 595 600 605 His Cys His Arg Asp Phe Lys Glu Glu Arg Pro Glu Glu Tyr Glu Ser 610 615 620 Trp Arg Glu Met Tyr Leu Arg Leu Gin Asp Ala Arg Glu Gin Arg Leu 625 630 635 640 Arg Leu Leu Thr Asn Asn He Arg Ser Ala His Ala Asn Lys Pro Lys 645 650 655 Gly Arg Gin Ala Lys Met Ala Phe Val Asn Ser Val Ala Lys Pro Pro 660 665 670 Arg Asp Val Arg Arg Arg Gin Glu Lys Phe Gly Thr Gly Gly Ala Ala 675 680 685 Val Pro Glu Lys Val Arg He Lys Pro Ala Pro Tyr Thr Thr Gly Ser 690 695 700 Ser His Val Pro Ala Ser Asn Ser Ser Ser Ser Phe His Ser Ser Pro 705 710 715 720 Glu Glu Leu Ala Tyr Glu Gly Pro Ser Thr Ser Ser Ala His Leu Ala 725 730 735 Pro Val Ala Ser Ser Ser Val Ser Tyr Asp Pro Arg Lys Pro Ala Val 740 745 750 Lys Lys He Ala Pro Met Met Ala Lys Thr He Lys Ala Phe Lys Asn 755 760 765 Arg Phe Ser Arg Arg * 770 (2) INFORMATION FOR SEQ ID NO:7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 444 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: cDNA to mRNA (vi) ORIGINAL SOURCE: (A) ORGANISM: Homo sapiens (F) TISSUE TYPE: Blood (G) CELL TYPE: Lymphocyte (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 88..426 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:7: AGATTTGGCA CGAGTCGGCA CGAGGCGGGA CTGACGAGAA ACTACTAAAG TTCCTGGGGA 60 AGCAAAGTAG AATTTCATAA GAACAAA ATG GAT GGA GAG GAG AAA ACC TAT 111 Met Asp Gly Glu Glu Lys Thr Tyr 1 5 GGT GGC TGT GAA GGA CCT GAT GCC ATG TAT GTC AAA TTG ATA TCA TCT 159 Gly Gly Cys Glu Gly Pro Asp Ala Met Tyr Val Lys Leu He Ser Ser 10 15 20 GAT GGC CAT GAA TTT ATT GTA AAA AGA GAA CAT GCA TTA ACA TCA GGC 207 Asp Gly His Glu Phe He Val Lys Arg Glu His Ala Leu Thr Ser Gly 25 30 35 40 ACG ATA AAA GCC ATG TTG AGT GGC CCA GGT CAG TTT GCT GAG AAC GAA 255 Thr He Lys Ala Met Leu Ser Gly Pro Gly Gin Phe Ala Glu Asn Glu 45 50 55 ACC AAT GAG GTC AAT TTT AGA GAG ATA CCT TCA CAT GTG CTA TCG AAA 303 Thr Asn Glu Val Asn Phe Arg Glu He Pro Ser His Val Leu Ser Lys 60 65 70 GTA TGC ATG TAT TTT ACG TAC AAG GTT CGC TAC ACT AAC AGC TCC ACC 351 Val Cys Met Tyr Phe Thr Tyr Lys Val Arg Tyr Thr Asn Ser Ser Thr 75 80 85 GAG ATT CCT GAA TTC CCA ATT GCA CCT GAA ATT GCA CTG GAA CTG CTG 399 Glu He Pro Glu Phe Pro He Ala Pro Glu He Ala Leu Glu Leu Leu 90 95 100 ATG GCT GCG AAC TTC TTA GAT TGT TAA ATAAAATAAA TTATAATA 444 Met Ala Ala Asn Phe Leu Asp Cys * 105 110 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 113 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:8: Met Asp Gly Glu Glu Lys Thr Tyr Gly Gly Cys Glu Gly Pro Asp Ala 1 5 10 15 Met Tyr Val Lys Leu He Ser Ser Asp Gly His Glu Phe He Val Lys 20 25 30 Arg Glu His Ala Leu Thr Ser Gly Thr He Lys Ala Met Leu Ser Gly 35 40 45 Pro Gly Gin Phe Ala Glu Asn Glu Thr Asn Glu Val Asn Phe Arg Glu 50 55 60 He Pro Ser His Val Leu Ser Lys Val Cys Met Tyr Phe Thr Tyr Lys 65 70 75 80 Val Arg Tyr Thr Asn Ser Ser Thr Glu He Pro Glu Phe Pro He Ala 85 90 95 Pro Glu He Ala Leu Glu Leu Leu Met Ala Ala Asn Phe Leu Asp Cys 100 105 110 (2) INFORMATION FOR SEQ ID NO:9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 357 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 1..357 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:9: ATG GAC GTG TTC CTC ATG ATC CGG CGC CAC AAG ACC ACC ATC TTC ACG 48 Met Asp Val Phe Leu Met He Arg Arg His Lys Thr Thr He Phe Thr 1 5 10 15 GAC GCC AAG GAG TCC AGC ACG GTG TTC GAA CTG AAG CGC ATC GTC GAG 96 Asp Ala Lys Glu Ser Ser Thr Val Phe Glu Leu Lys Arg He Val Glu 20 25 30 GGC ATC CTC AAG CGG CCT CCT GAC GAG CAG CGG CTG TAC AAG GAT GAC 144 Gly He Leu Lys Arg Pro Pro Asp Glu Gin Arg Leu Tyr Lys Asp Asp 35 40 45 CAA CTC TTG GAT GAT GGC AAG ACA CTG GGC GAG TGT GGC TTC ACC AGT 192 Gin Leu Leu Asp Asp Gly Lys Thr Leu Gly Glu Cys Gly Phe Thr Ser 50 55 60 CAA ACA GCA CGG CCA CAG GCC CCA GCC ACA GTG GGG CTG GCC TTC CGG 240 Gin Thr Ala Arg Pro Gin Ala Pro Ala Thr Val Gly Leu Ala Phe Arg 65 70 75 80 GCA GAT GAC ACC TTT GAG GCC CTG TGC ATC GAG CCG TTT TCC AGC CCG 288 Ala Asp Asp Thr Phe Glu Ala Leu Cys He Glu Pro Phe Ser Ser Pro 85 90 95 CCA GAG CTG CCC GAT GTG ATG AAG CCC CAG GAC TCG GGA AGC AGT GCC 336 Pro Glu Leu Pro Asp Val Met Lys Pro Gin Asp Ser Gly Ser Ser Ala 100 105 110 AAT GAA CAA GCC GTG CAG TGA 357 Asn Glu Gin Ala Val Gin * 115 (2) INFORMATION FOR SEQ ID NO:10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 119 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:10: Met Asp Val Phe Leu Met He Arg Arg His Lys Thr Thr He Phe Thr 1 5 10 15 Asp Ala Lys Glu Ser Ser Thr Val Phe Glu Leu Lys Arg He Val Glu 20 25 30 Gly He Leu Lys Arg Pro Pro Asp Glu Gin Arg Leu Tyr Lys Asp Asp 35 40 45 Gin Leu Leu Asp Asp Gly Lys Thr Leu Gly Glu Cys Gly Phe Thr Ser 50 55 60 Gin Thr Ala Arg Pro Gin Ala Pro Ala Thr Val Gly Leu Ala Phe Arg 65 70 75 80 Ala Asp Asp Thr Phe Glu Ala Leu Cys He Glu Pro Phe Ser Ser Pro 85 90 95 Pro Glu Leu Pro Asp Val Met Lys Pro Gin Asp Ser Gly Ser Ser Ala 100 105 110 Asn Glu Gin Ala Val Gin * 115 (2) INFORMATION FOR SEQ ID NO:11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2690 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: both (D) TOPOLOGY: both (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: CDS (B) LOCATION: 33..2351 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:11: GTTCCGGCGA GGAGGCCGCG CCAGTGACAG CG ATG GCG GCG GAG TCG GCG CTC S3 Met Ala Ala Glu Ser Ala Leu 1 5 CAA GTT GTG GAG AAG CTG CAG GCG CGC CTG GCC GCG AAC CCG GAC CCT 101 Gin Val Val Glu Lys Leu Gin Ala Arg Leu Ala Ala Asn Pro Asp Pro 10 15 20 AAG AAG CTA TTG AAA TAT TTG AAG AAA CTC TCC ACC CTG CCT ATT ACA 149 Lys Lys Leu Leu Lys Tyr Leu Lys Lys Leu Ser Thr Leu Pro He Thr 25 30 35 GTA GAC ATT CTT GCG GAG ACT GGG GTT GGG AAA ACA GTA AAT AGC TTG 197 Val Asp He Leu Ala Glu Thr Gly Val Gly Lys Thr Val Asn Ser Leu 40 45 50 55 CGA AAA CAC GAG CAT GTT GGA AGC TTT GCC AGG GAC CTA GTG GCC CAG 245 Arg Lys His Glu His Val Gly Ser Phe Ala Arg Asp Leu Val Ala Gin 60 65 70 TGG AAG AAG CTG GTT CCT GTG GAA CGA AAT GCT GAG CCT GAT GAA CAG 293 Trp Lys Lys Leu Val Pro Val Glu Arg Asn Ala Glu Pro Asp Glu Gin 75 80 85 GAC TTT GAG AAG AGC AAT TCC CGA AAG CGC CCT CGG GAT GCC CTG CAG 341 Asp Phe Glu Lys Ser Asn Ser Arg Lys Arg Pro Arg Asp Ala Leu Gin 90 95 100 AAG GAG GAG GAG ATG GAG GGG GAC TAC CAA GAA ACC TGG AAA GCC ACG 389 Lys Glu Glu Glu Met Glu Gly Asp Tyr Gin Glu Thr Trp Lys Ala Thr 105 110 115 GGG AGC CGA TCC TAT AGC CCT GAC CAC AGG CAG AAG AAA CAT AGG AAA 437 Gly Ser Arg Ser Tyr Ser Pro Asp His Arg Gin Lys Lys His Arg Lys 120 125 130 135 CTC TCG GAG CTC GAG AGA CCT CAC AAA GTG TCT CAC GGT CAT GAG AGG 485 Leu Ser Glu Leu Glu Arg Pro His Lys Val Ser His Gly His Glu Arg 140 145 150 AGA GAT GAG AGA AAG AGG TGT CAC AGA ATG TCA CCA ACT TAC TCT TCA 533 Arg Asp Glu Arg Lys Arg Cys His Arg Met Ser Pro Thr Tyr Ser Ser 155 160 165 GAC CCT GAG TCT TCT GAT TAT GGC CAT GTT CAA TCC CCT CCA TCT TGT 581 Asp Pro Glu Ser Ser Asp Tyr Gly His Val Gin Ser Pro Pro Ser Cys 170 175 180 ACC AGT CCT CAT CAG ATG TAC GTC GAC CAC TAC AGA TCC CTG GAG GAG 629 Thr Ser Pro His Gin Met Tyr Val Asp His Tyr Arg Ser Leu Glu Glu 185 190 195 GAC CAG GAG CCC ATT GTT TCA CAC CAG AAG CCT GGG AAA GGC CAC AGC 677 Asp Gin Glu Pro He Val Ser His Gin Lys Pro Gly Lys Gly His Ser 200 205 210 215 AAT GCC TTT CAG GAC AGA CTC GGG GCC AGC CAA GAA CGA CAC CTG GGT 725 Asn Ala Phe Gin Asp Arg Leu Gly Ala Ser Gin Glu Arg His Leu Gly 220 225 230 GAA CCC CAT GGG AAA GGG GTT GTG AGT CAA AAC AAG GAG CAC AAA TCT 773 Glu Pro His Gly Lys Gly Val Val Ser Gin Asn Lys Glu His Lys Ser 235 240 245 TCC CAC AAG GAC AAA CGC CCC GTG GAT GCC AAG AGT GAT GAG AAG GCC 821 Ser His Lys Asp Lys Arg Pro Val Asp Ala Lys Ser Asp Glu Lys Ala 250 255 260 TCT GTG GTG AGC AGA GAG AAA TCA CAC AAG GCC CTC TCC AAA GAG GAG 869 Ser Val Val Ser Arg Glu Lys Ser His Lys Ala Leu Ser Lys Glu Glu 265 270 275 AAC CGA AGG CCA CCC TCA GGG GAC AAT GCA AGG GAG AAA CCG CCC TCT 917 Asn Arg Arg Pro Pro Ser Gly Asp Asn Ala Arg Glu Lys Pro Pro Ser 280 285 290 295 AGT GGC GTA AAG AAA GAG AAG GAC AGA GAG GGC AGC AGC CTG AAG AAG 965 Ser Gly Val Lys Lys Glu Lys Asp Arg Glu Gly Ser Ser Leu Lys Lys 300 305 310 AAG TGT TTG CCT CCC TCA GAG GCC GCT TCA GAC AAC CAC CTG AAA AAG 1013 Lys Cys Leu Pro Pro Ser Glu Ala Ala Ser Asp Asn His Leu Lys Lys 315 320 325 CCA AAG CAC AGA GAC CCA GAG AAA GCC AAA TTG GAC AAA AGC AAG CAA 1061 Pro Lys His Arg Asp Pro Glu Lys Ala Lys Leu Asp Lys Ser Lys Gin 330 335 340 GGT CTG GAC. AGC TTT GAC ACA GGA AAA GGA GCA GGA GAC CTG TTG CCC 1109 Gly Leu Asp Ser Phe Asp Thr Gly Lys Gly Ala Gly Asp Leu Leu Pro 345 350 355 AAG GTA AAA GAG AAG GGT TCT AAC AAC CTA AAG ACT CCA GAA GGG AAA 1157 Lys Val Lys Glu Lys Gly Ser Asn Asn Leu Lys Thr Pro Glu Gly Lys 360 365 370 375 GTC AAA ACT AAT TTG GAT AGA AAG TCA CTG GGC TCC CTC CCT AAA GTT 1205 Val Lys Thr Asn Leu Asp Arg Lys Ser Leu Gly Ser Leu Pro Lys Val 380 385 390 GAG GAG ACA GAT ATG GAG GAT GAA TTC GAG CAG CCA ACC ATG TCT TTT 1253 Glu Glu Thr Asp Met Glu Asp Glu Phe Glu Gin Pro Thr Met Ser Phe 395 400 405 GAA TCC TAC CTC AGC TAT GAC CAG CCC CGG AAG AAA AAG AAA AAG ATT 1301 Glu Ser Tyr Leu Ser Tyr Asp Gin Pro Arg Lys Lys Lys Lys Lys He 410 415 420 GTG AAA ACT TCA GCC ACG GCA CTT GGA GAT AAA GGA CTT AAA AAA AAT 1349 Val Lys Thr Ser Ala Thr Ala Leu Gly Asp Lys Gly Leu Lys Lys Asn 425 430 435 GAC TCT AAA AGC ACT GGT AAA AAC TTG GAC TCA GTT CAG AAA TTA CCC 1397 Asp Ser Lys Ser Thr Gly Lys Asn Leu Asp Ser Val Gin Lys Leu Pro 440 445 450 455 AAG GTG AAC AAA ACC AAG TCA GAG AAG CCG GCT GGA GCT GAT TTA GCC 1445 Lys Val Asn Lys Thr Lys Ser Glu Lys Pro Ala Gly Ala Asp Leu Ala 460 465 470 AAG CTG AGA AAG GTG CCT GAT GTG TTG CCA GTG TTG CCA GAC CTC CCG 1493 Lys Leu Arg Lys Val Pro Asp Val Leu Pro Val Leu Pro Asp Leu Pro 475 480 485 TTA CCC GCG ATA CAG GCC AAT TAC CGT CCA CTG CCT TCC CTC GAG CTG 1541 Leu Pro Ala He Gin Ala Asn Tyr Arg Pro Leu Pro Ser Leu Glu Leu 490 495 500 ATA TCC TCC TTC CAG CCA AAG CGA AAA GCG TTC TCT TCA CCC CAG GAA 1589 He Ser Ser Phe Gin Pro Lys Arg Lys Ala Phe Ser Ser Pro Gin Glu 505 510 515 GAA GAA GAA GCT GGA TTT ACT GGG CGC AGA ATG AAT TCC AAG ATG CAG 1637 Glu Glu Glu Ala Gly Phe Thr Gly Arg Arg Met Asn Ser Lys Met Gin 520 525 530 535 GTG TAT TCT GGT TCC AAG TGT GCC TAT CTC CCT AAA ATG ATG ACC TTG 1685 Val Tyr Ser Gly Ser Lys Cys Ala Tyr Leu Pro Lys Met Met Thr Leu 540 545 550 CAC CAG CAA TGC ATC CGA GTA CTT AAA AAC AAC ATC GAT TCA ATC TTT 1733 His Gin Gin Cys He Arg Val Leu Lys Asn Asn He Asp Ser He Phe 555 560 565 GAA GTG GGA GGA GTC CCA TAC TCT GTT CTT GAA CCC GTT TTG GAG AGG 1781 Glu Val Gly Gly Val Pro Tyr Ser Val Leu Glu Pro Val Leu Glu Arg 570 575 580 TGT ACA CCT GAT CAG CTG TAT CGC ATA GAG GAA TAC AAT CAT GTA TTA 1829 Cys Thr Pro Asp Gin Leu Tyr Arg He Glu Glu Tyr Asn His Val Leu 585 590 595 ATT GAA GAA ACA GAT CAA TTA TGG AAA GTT CAT TGT CAC CGA GAC TTT 1877 He Glu Glu Thr Asp Gin Leu Trp Lys Val His Cys His Arg Asp Phe 600 605 610 615 AAG GAA GAA AGA CCC GAA GAG TAT GAG TCG TGG CGA GAG ATG TAC CTG 1925 Lys Glu Glu Arg Pro Glu Glu Tyr Glu Ser Trp Arg Glu Met Tyr Leu 620 625 630 CGG CTT CAG GAC GCC CGA GAG CAG CGG CTA CGA GTA CTA ACA AAG AAT 1973 Arg Leu Gin Asp Ala Arg Glu Gin Arg Leu Arg Val Leu Thr Lys Asn 635 640 645 ATC CAG TTC GCA CAT GCC AAT AAG CCC AAA GGC CGA CAA GCA AAG ATG 2021 He Gin Phe Ala His Ala Asn Lys Pro Lys Gly Arg Gin Ala Lys Met 650 655 660 GCC TTT GTC AAC TCT GTG GCC AAG CCA CCT CGT GAC GTC CGG AGG AGG 2069 Ala Phe Val Asn Ser Val Ala Lys Pro Pro Arg Asp Val Arg Arg Arg 665 670 675 CAG GAA AAG TTT GGA ACG GGA GGA GCA GCT GTC CCT GAG AAA ATC AAG 2117 Gin Glu Lys Phe Gly Thr Gly Gly Ala Ala Val Pro Glu Lys He Lys 680 685 690 695 ATC AAG CCA GCC CCG TAC CCC ATG GGA AGC AGC CAT GCT TCC GCC AGT 2165 He Lys Pro Ala Pro Tyr Pro Met Gly Ser Ser His Ala Ser Ala Ser 700 705 710 AGC ATC AGC TTT AAC CCC AGC CCT GAG GAG CCG GCC TAT GAT GGC CCA 2213 Ser He Ser Phe Asn Pro Ser Pro Glu Glu Pro Ala Tyr Asp Gly Pro 715 720 725 AGC ACC AGC AGT GCC CAC TTG GCA CCA GTG GTC AGC AGC ACT GTT TCC 2261 Ser Thr Ser Ser Ala His Leu Ala Pro Val Val Ser Ser Thr Val Ser 730 735 740 TAT GAT CCT AGG AAA CCC ACT GTG AAG AAA ATT GCC CCA ATG ATG GCC 2309 Tyr Asp Pro Arg Lys Pro Thr Val Lys Lys He Ala Pro Met Met Ala 745 750 755 AAG ACA ATT AAA GCT TTC AAG AAC AGA TTC TCC CGA CGA TAA 2351 Lys Thr He Lys Ala Phe Lys Asn Arg Phe Ser Arg Arg * 760 765 770 ACTGAGGACT TGCCTTGGAA ATGGAATCTG GGGAGGCAGG AATACAAGGA CAGTGGGGGT 2411 TGGGGAATGG AATTCTACAG GAGACTGGAG TCTTGCTTTG TGGATCCTTT TGGTCTCCGA 2471 GTCTGCAGTC TGCAGGTGCT GCCCCTGGGA ACCTGCGTGC CACAGCCCCG CCTCCCTGCC 2531 TGGAGCACAC TTTAGAATTC TGAAGATGTG AAGCCTCTGT CTCACTGAGG ATTTTAAAGG 2591 TCAATTATAC TTTTGTTGTT CATTAGCATC TTTGTAAACT ATAAGACGTA GTTTTAATTA 2651 ATAAATATTG CCCCCAGATG TTAAAAAAAA AAAAAAAAA 2690 (2) INFORMATION FOR SEQ ID NO:12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 773 amino acids (B) TYPE: amino acid (D) TOPOLOGY: linear (ii) MOLECULE TYPE: protein (xi) SEQUENCE DESCRIPTION: SEQ ID NO:12: Met Ala Ala Glu Ser Ala Leu Gin Val Val Glu Lys Leu Gin Ala Arg 1 5 10 15 Leu Ala Ala Asn Pro Asp Pro Lys Lys Leu Leu Lys Tyr Leu Lys Lys 20 25 30 Leu Ser Thr Leu Pro He Thr Val Asp He Leu Ala Glu Thr Gly Val 35 40 45 Gly Lys Thr Val Asn Ser Leu Arg Lys His Glu His Val Gly Ser Phe 50 55 60 Ala Arg Asp Leu Val Ala Gin Trp Lys Lys Leu Val Pro Val Glu Arg 65 70 75 80 Asn Ala Glu Pro Asp Glu Gin Asp Phe Glu Lys Ser Asn Ser Arg Lys 85 90 95 Arg Pro Arg Asp Ala Leu Gin Lys Glu Glu Glu Met Glu Gly Asp Tyr 100 105 110 Gin Glu Thr Trp Lys Ala Thr Gly Ser Arg Ser Tyr Ser Pro Asp His 115 120 125 Arg Gin Lys Lys His Arg Lys Leu Ser Glu Leu Glu Arg Pro His Lys 130 135 140 Val Ser His Gly His Glu Arg Arg Asp Glu Arg Lys Arg Cys His Arg 145 150 155 160 Met Ser Pro Thr Tyr Ser Ser Asp Pro Glu Ser Ser Asp Tyr Gly His 165 170 175 Val Gin Ser Pro Pro Ser Cys Thr Ser Pro His Gin Met Tyr Val Asp 180 185 190 His Tyr Arg Ser Leu Glu Glu Asp Gin Glu Pro He Val Ser His Gin 195 200 205 Lys Pro Gly Lys Gly His Ser Asn Ala Phe Gin Asp Arg Leu Gly Ala 210 215 220 Ser Gin Glu Arg His Leu Gly Glu Pro His Gly Lys Gly Val Val Ser 225 230 235 240 Gin Asn Lys Glu His Lys Ser Ser His Lys Asp Lys Arg Pro Val Asp 245 250 255 Ala Lys Ser Asp Glu Lys Ala Ser Val Val Ser Arg Glu Lys Ser His 260 265 270 Lys Ala Leu Ser Lys Glu Glu Asn Arg Arg Pro Pro Ser Gly Asp Asn 275 280 285 Ala Arg Glu Lys Pro Pro Ser Ser Gly Val Lys Lys Glu Lys Asp Arg 290 295 300 Glu Gly Ser Ser Leu Lys Lys Lys Cys Leu Pro Pro Ser Glu Ala Ala 305 310 315 320 Ser Asp Asn His Leu Lys Lys Pro Lys His Arg Asp Pro Glu Lys Ala 325 330 335 Lys Leu Asp Lys Ser Lys Gin Gly Leu Asp Ser Phe Asp Thr Gly Lys 340 345 350 Gly Ala Gly Asp Leu Leu Pro Lys Val Lys Glu Lys Gly Ser Asn Asn 355 360 365 Leu Lys Thr Pro Glu Gly Lys Val Lys Thr Asn Leu Asp Arg Lys Ser 370 375 380 Leu Gly Ser Leu Pro Lys Val Glu Glu Thr Asp Met Glu Asp Glu Phe 385 390 395 400 Glu Gin Pro Thr Met Ser Phe Glu Ser Tyr Leu Ser Tyr Asp Gin Pro 405 410 415 Arg Lys Lys Lys Lys Lys He Val Lys Thr Ser Ala Thr Ala Leu Gly 420 425 430 Asp Lys Gly Leu Lys Lys Asn Asp Ser Lys Ser Thr Gly Lys Asn Leu 435 440 445 Asp Ser Val Gin Lys Leu Pro Lys Val Asn Lys Thr Lys Ser Glu Lys 450 455 460 Pro Ala Gly Ala Asp Leu Ala Lys Leu Arg Lys Val Pro Asp Val Leu 465 470 475 480 Pro Val Leu Pro Asp Leu Pro Leu Pro Ala He Gin Ala Asn Tyr Arg 485 490 495 Pro Leu Pro Ser Leu Glu Leu He Ser Ser Phe Gin Pro Lys Arg Lys 500 505 510 Ala Phe Ser Ser Pro Gin Glu Glu Glu Glu Ala Gly Phe Thr Gly Arg 515 520 525 Arg Met Asn Ser Lys Met Gin Val Tyr Ser Gly Ser Lys Cys Ala Tyr 530 535 540 Leu Pro Lys Met Met Thr Leu His Gin Gin Cys He Arg Val Leu Lys 545 550 555 560 Asn Asn He Asp Ser He Phe Glu Val Gly Gly Val Pro Tyr Ser Val 565 570 575 Leu Glu Pro Val Leu Glu Arg Cys Thr Pro Asp Gin Leu Tyr Arg He 580 585 590 Glu Glu Tyr Asn His Val Leu He Glu Glu Thr Asp Gin Leu Trp Lys 595 600 605 Val His Cys His Arg Asp Phe Lys Glu Glu Arg Pro Glu Glu Tyr Glu 610 615 620 Ser Trp Arg Glu Met Tyr Leu Arg Leu Gin Asp Ala Arg Glu Gin Arg 625 630 635 640 Leu Arg Val Leu Thr Lys Asn He Gin Phe Ala His Ala Asn Lys Pro 645 650 655 Lys Gly Arg Gin Ala Lys Met Ala Phe Val Asn Ser Val Ala Lys Pro 660 665 670 Pro Arg Asp Val Arg Arg Arg Gin Glu Lys Phe Gly Thr Gly Gly Ala 675 680 685 Ala Val Pro Glu Lys He Lys He Lys Pro Ala Pro Tyr Pro Met Gly 690 695 700 Ser Ser His Ala Ser Ala Ser Ser He Ser Phe Asn Pro Ser Pro Glu 705 710 715 720 Glu Pro Ala Tyr Asp Gly Pro Ser Thr Ser Ser Ala His Leu Ala Pro 725 730 735 Val Val Ser Ser Thr Val Ser Tyr Asp Pro Arg Lys Pro Thr Val Lys 740 745 750 Lys He Ala Pro Met Met Ala Lys Thr He Lys Ala Phe Lys Asn Arg 755 760 765 Phe Ser Arg Arg * 770 (2) INFORMATION FOR SEQ ID NO:13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 13 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:13: Leu He Ser Ser Asp Gly His Glu Phe He Val Lys Arg 1 5 10 (2) INFORMATION FOR SEQ ID NO:14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:14: Ala Met Leu Ser Gly Pro Gly Gin Phe Ala Glu Asn Glu Thr Asn Glu 1 5 10 15 Val Asn Phe Arg 20 (2) INFORMATION FOR SEQ ID NO:15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 8 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:15: Val Cys Met Tyr Phe Thr Tyr Lys 1 5 (2) INFORMATION FOR SEQ ID NO:16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:16: Tyr Thr Asn Ser Ser Thr Glu He Pro Glu Phe Pro He Ala Pro Glu 1 5 10 15 He Ala Leu Glu Leu Leu Met Ala Ala Asn Phe Leu Asp 20 25 (2) INFORMATION FOR SEQ ID NO:17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 1..20 (D) OTHER INFORMATION: /note= "degenerate oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:17: CARTTYGCNG ARAAYGARAC 20 (2) INFORMATION FOR SEQ ID NO:18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 1..20 (D) OTHER INFORMATION: /note= "degenerate oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:18: GGNGCDATNG GRAAYTCNGG 20 (2) INFORMATION FOR SEQ ID NO:19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE : cDNA (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 1..20 (D) OTHER INFORMATION: /note= "degenerate oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:19: ACNAAYGARG TNAAYTTYMG 20 (2) INFORMATION FOR SEQ ID NO:20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:20: Leu Tyr Lys Asp Asp Gin Leu Leu Asp Asp Gly Lys Thr Leu Gly Glu 1 5 10 15 Cys Gly Phe Thr Ser Gin Thr Ala Arg Pro Gin Ala Pro 20 25 (2) INFORMATION FOR SEQ ID NO:21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: Ala Asp Asp Thr Gly Glu Ala Leu Arg He Glu Pro Phe Ser Ser Pro 1 5 10 15 Pro Glu Leu Pro Asp Val Met Lys Pro Gin Asp Ser Gly Gly Ser Ala 20 25 30 Asn Glu (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 1..19 (D) OTHER INFORMATION: /note= "degenerate oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:22: TNTAYAARGA YGAYCARYT 19 (2) INFORMATION FOR SEQ ID NO:23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 1..20 (D) OTHER INFORMATION: /note= "degenerate oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:23: TGNGGYTTCA TNACRTCNGG 20 (2) INFORMATION FOR SEQ ID NO:24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: misc_feature (B) LOCATION: 1..20 (D) OTHER INFORMATION: /note= "degenerate oligonucleotide" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:24: GCNGAYGAYA CNTTYGARGC 20 (2) INFORMATION FOR SEQ ID NO:25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:25: Asp Val Pro Gin Gin Glu Glu Glu Ala Glu Gly Asn Tyr Gin Glu Ser 1 5 10 15 Trp Gin Ala Ser Gly Ser Gin Pro Tyr Tyr Pro Glu His Arg 20 25 30 (2) INFORMATION FOR SEQ ID NO:26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:26: Ala Asn Glu Asn Lys Ser Asp Lys Leu Gin Pro Ala Gly Ala Glu Pro 1 5 10 15 Thr Arg Pro (2) INFORMATION FOR SEQ ID NO:27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 43 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 12 (D) OTHER INFORMATION : /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 17 (D) OTHER INFORMATION: /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 35 (D) OTHER INFORMATION: /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 38 (D) OTHER INFORMATION: /mod_base= i (xi) SEQUENCE DESCRIPTION: SEQ ID NO:27: TCCTGGTAGT TNCCTCNGCC TCCTCCTCCT GCTGNGGNAC GTC 43 (2) INFORMATION FOR SEQ ID NO:28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 29 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 9 (D) OTHER INFORMATION: /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 15 (D) OTHER INFORMATION: /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 18 (D) OTHER INFORMATION: /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 21 (D) OTHER INFORMATION: /mod_base= i (ix) FEATURE: (A) NAME/KEY: modified_base (B) LOCATION: 24 (D) OTHER INFORMATION: /mod_base= i (xi) SEQUENCE DESCRIPTION: SEQ ID NO:28: CGGATCGTNG GYTCNGCNCC NGCNGGYTG 29 (2) INFORMATION FOR SEQ ID NO:29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:29: CGTAATACGA CTCACTATAG GG 22 (2) INFORMATION FOR SEQ ID NO:30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:30: Met His His His His His His Asn Val Asp 1 5 10 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: peptide (xi) SEQUENCE DESCRIPTION: SEQ ID NO:31: Met His His His His His His Asn Val Asp 1 5 10 (2) INFORMATION FOR SEQ ID NO:32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (Xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: GCAGCGGATC CTCAACAATC TAGGAAGTTC G 31 (2) INFORMATION FOR SEQ ID NO:33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: CDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:33: GCAACGTCGA CATGGACGTG TTTCTCATGA T 31 (2) INFORMATION FOR SEQ ID NO:34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 31 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:34: GCAGCGGATC CTCACTGCAC AGCTTGTTCA T 31 (2) INFORMATION FOR SEQ ID NO-.35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: GCNGAYGAYA CNTTYGARGC 20 (2) INFORMATION FOR SEQ ID NO:36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:36: GCTTTCTCCC TTGCATTGTC CC 22 (2) INFORMATION FOR SEQ ID NO:37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO:37: CCTCTAGAAT TTCTCTCTGC TCACCACAGG 30

Claims: WE CLAIM : 1. A substantially purified RNA polymerase transcription factor known as Elongin. 2. The transcription factor of claim 1 wherein said transcription factor has a molecular weight of approximately 140 kilodaltons. 3. The transcription factor of claim 2 wherein said transcription factor is a heterotrimeric protein comprising a single copy each of: a) a first subunit having a molecular weight of approximately 110 kilodaltons; b) a second subunit having a molecular weight of approximately 18 kilodaltons; and c) a third subunit having a molecular weight of approximately 15 kilodaltons. 4. The transcription factor of claim 3 wherein the approximately 15, 18 and 110 kilodalton subunits comprise an amino acid sequence as depicted in SEQ ID NO:2, SEQ ID NO:4, and SEQ ID NO:6, respectively. 5. The transcription factor of claim 4 wherein the approximately 15, 18 and 110 kilodalton subunits comprise an amino acid sequence as depicted in SEQ ID NO:8, SEQ ID NO:10 and SEQ ID NO:12, respectively. 6. A substantially purified subunit of Elongin. 7. The substantially purified subunit of claim 6 wherein said subunit has a molecular weight of approximately 15 kilodaltons. 8. The substantially purified subunit of claim 7 wherein said subunit comprises an amino acid sequence as depicted in SEQ ID NO:2. 9. The substantially purified subunit of claim 7 wherein said subunit comprises an amino acid sequence as in SEQ ID NO:8. 10. The substantially purified subunit of claim 6 wherein said subunit has a molecular weight of approximately 18 kilodaltons. 11. The substantially purified subunit of claim 10 wherein said subunit comprises an amino acid sequence as depicted in SEQ ID NO:4. 12. The substantially purified subunit of claim 10 wherein said subunit comprises an amino acid sequence as depicted in SEQ ID NO:10. 13. The substantially purified subunit of claim 6 wherein said subunit has a molecular weight of approximately 110 kilodaltons. 14. The substantially purified subunit of claim 13 wherein said subunit comprises an amino acid sequence as depicted in SEQ ID NO:6. 15. The substantially purified subunit of claim 13 wherein said subunit comprises an amino acid sequence as depicted in SEQ ID NO:12. 16. A process for purifying Elongin which comprises: a. isolating proteins from eukaryotic cells; and b. fractionating, concentrating and purifying Elongin activity. 17. The process of claim 16 wherein said eukaryotic cells are liver cells. 18. The process of claim 16 wherein said eukaryotic cells are brain cells. 19. The process of claim 16 wherein said eukaryotic cells are peripheral blood lymphocytes. 20. The process of claim 16 wherein said eukaryotic cells are umbilical vein endothelial cells. 21. A nucleic acid fragment comprising a nucleotide sequence encoding an approximately 15 kilodalton subunit of Elongin. 22. The nucleic acid fragment of claim 21 wherein the nucleotide sequence encoding the approximately 15 kilodalton subunit comprises nucleotides 46 to 381 in SEQ ID NO:l, or any nucleic acid fragment substantially homologous therewith. 23. The nucleic acid fragment of claim 21 wherein the nucleotide sequence encoding the approximately 15 kilodalton subunit comprises nucleotides 88 to 423 in SEQ ID NO:7, or any nucleic acid fragment substantially homologous therewith. 24. A nucleic acid fragment comprising a nucleotide sequence encoding an approximately 18 kilodalton subunit of Elongin. 25. The nucleic acid fragment of claim 24 wherein the nucleotide sequence encoding the approximately 18 kilodalton subunit comprises nucleotides 1 to 354 in SEQ ID NO:3, or any nucleic acid fragment substantially homologous therewith. 26. The nucleic acid fragment of claim 24 wherein the nucleotide sequence encoding the approximately 18 kilodalton subunit comprises nucleotides 1 to 354 in SEQ ID NO:9, or any nucleic acid fragment substantially homologous therewith. 27. A nucleic acid fragment comprising a nucleotide sequence encoding an approximately 110 kilodalton subunit of Elongin. 28. The nucleic acid fragment of claim 27 wherein the nucleotide sequence encoding the approximately 110 kilodalton subunit comprises nucleotides 82 to 2400 in SEQ ID NO:5, or any nucleic acid fragment substantially homologous therewith. 29. The nucleic acid fragment of claim 27 wherein the nucleotide sequence encoding the approximately 110 kilodalton subunit comprises nucleotides 53 to 2348 in SEQ ID NO:11, or any nucleic acid fragment substantially homologous therewith. 30. A nucleic acid fragment comprising a nucleotide sequence encoding a transcriptionally active fragment of an approximately 110 kilodalton subunit of Elongin. 31. The nucleic acid fragment of claim 30 wherein the nucleotide sequence encoding the transcriptionally active fragment of the approximately 110 kilodalton submit of Elongin comprises nucleotides 1279 to 2121 in SEQ ID NO:5. 32. The nucleic acid fragment of claim 31 wherein the nucleotide sequence encoding the transcriptionally active fragment of the approximately 110 kilodalton submit of Elongin comprises nucleotides 1232 to 2072 in SEQ ID NO:11. 33. A process of modulating the transcription rate of RNA polymerase II comprising varying the concentration of Elongin available to RNA polymerase II during transcription. 34. The process of claim 33 wherein said modulation occurs in vi tro. 35. A process which comprises expressing a DNA sequence encoding Elongin in a recombinant host transformed with an expression vector containing said DNA sequence. 36. The process according to claim 35 wherein said DNA is in the antisense orientation. 37. A process which comprises expressing a DNA sequence encoding a subunit of Elongin in a recombinant host transformed with an expression vector containing said DNA sequence. 38. The process according to claim 37 wherein said DNA is in the antisense orientation. 39. A recombinant DNA molecule capable of functioning as a vector comprising a nucleotide sequence encoding an approximately 15 kilodalton subunit of Elongin. 40. The recombinant DNA molecule of claim 39 wherein the nucleotide sequence encoding the approximately 15 kilodalton subunit comprises nucleotides 46 to 381 in SEQ ID NO:l, or any nucleic acid fragment substantially homologous therewith. 41. The recombinant DNA molecule of claim 40 wherein the nucleotide sequence encoding the approximately 15 kilodalton subunit comprises nucleotides 88 to 423 in SEQ ID NO:7, or any nucleic acid fragment substantially homologous therewith. 42. A recombinant DNA molecule capable of functioning as a vector comprising a nucleotide sequence encoding an approximately 18 kilodalton subunit of Elongin. 43. The recombinant DNA molecule of claim 42 wherein the nucleotide sequence encoding the approximately 18 kilodalton subunit comprises nucleotides 1 to 354 in SEQ ID NO:3, or any nucleic acid fragment substantially homologous therewith. 44. The recombinant DNA molecule of claim 32 wherein the nucleotide sequence encoding the approximately 18 kilodalton subunit comprises nucleotides 1 to 354 in SEQ ID NO:9, or any nucleic acid fragment substantially homologous therewith. 45. An expression vector comprising a nucleotide sequence encoding an approximately 110 kilodalton subunit of Elongin. 46. The expression vector of claim 45 wherein the nucleotide sequence encoding the approximately 110 kilodalton subunit comprises nucleotides 82 to 2400 in SEQ ID NO:5, or any nucleic acid fragment substantially homologous therewith. 47. The expression vector of claim 45 wherein the nucleotide sequence encoding the approximately 110 kilodalton subunit comprises nucleotides 53 to 2348 in SEQ ID NO:11, or any nucleic acid fragment substantially homologous therewith. 48. An expression vector comprising a nucleotide sequence encoding a transcriptionally active fragment of an approximately 110 kilodalton subunit of Elongin. 49. The expression vector of claim 48 wherein the nucleotide sequence encoding the transcriptionally active fragment of the approximately 110 kilodalton subunit of Elongin comprises nucleotides 1279 to 2121 in SEQ ID NO:5. 50. The expression vector of claim 48 wherein the nucleotide sequence encoding the transcriptionally active fragment of the approximately 110 kilodalton subunit of Elongin comprises nucleotides 1232 to 2072 in SEQ ID NO:11. 51. A probe corresponding to less than the entire DNA sequence encoding a subunit of Elongin.

Inventors: BRADSHER JOHN N, CONAWAY JOAN W, CONAWAY RONALD C, BRADSHER, JOHN, N., CONAWAY, JOAN, W., CONAWAY, RONALD, C.
Applicants: OKLAHOMA MED RES FOUND, OKLAHOMA MEDICAL RESEARCH FOUNDATION
Application year: 1996
Main classification: C12N15
IPC codes: C07K1, C07K14, C12N1, C12N5, C12N15, C12Q1