Patent ID: 6706491
Filing Date: 2004-03-16
Classification: A61P,C07K

Abstract:
A method for identifying a compound that inhibits p21-mediated modulation of cellular gene expression, the method comprising the steps of:(a) inducing overexpression of p21 in a mammalian cell, (b) assaying the cell in the presence and absence of the compound for changes in expression of a cellular gene whose expression is modulated by p21, wherein the cellular gene is CDC2 (Acc. No. X05360), CKsHs1 (CDC2 kinase)(Acc. No. X54941), PLk1 (polo-like kinase) (Acc. No. U01038), XCAP-H condensin homolog (Acc. No. D38553), CENP-A (centromere protein A) (Acc. No. U14518), CENP-F (centromere protein F) (Acc. No. U30872), MAD2 (Acc. No. U65410), BUBR1 (Acc. No. AF053306), MCAK (mitotic centromere-associated kinesin) (Acc. No. U63743), HSET kinesin-like protein (Acc. No. AL021366), CHL1 helicase (Acc. No. U75968), AIK-1 (auror-a/IPL1-related kinase) (Acc. No. D84212), AIM-1 (AIK-2; aurora/IPL1-related kinase) (Acc. No. AF004022), PRC1 (protein regulating cytokinesis 1) (Acc. No. AF044588), Citron kinase (Acc. No. H10809), Lamin B1 (Acc. No. L37747), Lamin B2 (Acc. No. M94362), LAP-2 (lamin-associated protein 2) (Acc. No. U18271), MPP2 (M phase phosphoprotein 2) (Acc. No. U74612), MPP5 (M phase phosphoprotein 5) (Acc. No. X98261), Thymidine kinase 1 (Acc. No. K02581), Thymidylate synthase (Acc. No. X02308), Uridine phosphorylase (Acc. No. X90858), Ribonucleotide reductase M1 (Acc. No. X59543), Ribonucleotide reductase M2 (Acc. No. X59618), CDC47 homolog (MCM7) (Acc. No. D55716) CDC21 homolog (MCM4) (Acc. No. X74794), CDC45 homolog (Porc-PI) (Acc. No. AJ223728), HsORC1 (origin recognition complex 1) (Acc. No. U40152), DNA polymerase &agr; (Acc. No. X06745), Replication factor C (37-kD subunit) (Acc. No. M87339), B-MYB (Acc. No. X13293), HPV16 E1 protein binding protein (Acc. No. U96131), Topoisomerase II&agr; (Acc. No. J04088), Chromatin assembly factor-1 (p60 subunit) (Acc. No. U20980), High-mobility group chromosomal protein 2 (Acc. No. X62534), High-mobility group chromosomal protein 1 (Acc. No. D63874), Histone H2A.F/Z variant (Acc. No. AA203494), XRCC9 (Acc. No. U70310), RAD54 homolog (Acc. No. X97795), HEX1 5â€²-3â€²exonuclease (RAD2 homolog) (Acc. No. AF042282), ATP-dependent DNA ligase I (Acc. No. M36067), RAD21 homolog (Acc. No. D38551 ), Putative transcription factor CA150 (Acc. No. AF017789), Transcriptional coactivator ALY (Acc. No. AF047002), WHSC1/MMSET (SET domain protein) (Acc. No. AA401245), NN8-4AG (SET domain protein) (Acc. No. U50383), EZH2 (enhancer of zeste homolog 2) (Acc. No. U61145), PTB-associated splicing factor (Acc. No. X70944), AU-rich element RNA-binding protein AUF1 (Acc. No. U02019), U-snRNP-associated cyclophilin (Acc. No. AF016371), 3-phosphoglycerate dehydrogenase (Acc. No. AF006043), L-type amino acid transporter, subunit LAT1 (Acc. No. M80244), Hyaluronan-mediated motility receptor (Acc. No. U29343), Phorbolin I (PKC-inducible) (Acc. No. U03891), PSD-95 binding family protein (Acc. No. D13633), HTRIP (TNF receptor component) (Acc. No. U77845), NAD-dependent methylenetetrahydrofolate dehydrogenase (Acc. No. X16396), Membrane glycoprotein 4F2 antigen heavy chain (Acc. No. J02939), Mucin-like protein (Acc. No. 079992), M:AC30 (differentially expressed in meningiomas) (Acc. No. L19183), P52rIPK (regulator of interferon-induced protein kinase) (Acc. No. AF007393), Putative phosphoserine aminotransferase (Acc. No. AA192483), Glucose 6-phosphate translocase (Acc. No. Y15409), Calcyclin binding protein (Acc. No. AF057356), Ornithine decarboxylase 1 (Acc. No. X16277), Trophinin assisting protein (tastin) (Acc. No. U04810), Acyl-coenzyme A cholesterol acyltransferase (Acc. No. L21934), Pinin/SDK3 (Acc. No. Y10351), EST (Acc. No. AA975298), EST (Acc. No. AA034414), EST (Acc. No. AA482549) Cyclin A1 (Acc. No. U66838), Cyclin B1 (Acc. No. M25753), CDC25A (Acc. No. NM001789), Dihydrofolate reductase (Acc. No. J00140), or ING1 (Acc. No. NM 005537), Fibronectin 1 (Acc. No. X02761), Plasminogen activator inhibitor, type I (Acc. No. M14083), Plasminogen activator, tissue type (Acc. No. M15518), Laminin &bgr;2 (Acc. No. X79683), Desmocollin 2a/bb (Acc. No. X56807), Podocalyxin-like protein (Acc. No. U97519), Activin A (inhibin &bgr;A) (Acc. No. J03634), Galectin 3 (Mac-2) (Acc. No. AB006780), Mac-2 binding protein (Acc. No. L13210), Prosaposin (Acc. No. J03077), CTGF (connective tissue growth factor) (Acc. No. M92934), Granulin/epithelin (Acc. No. AF055008), Cathepsin B (Acc. No. L04288), Tissue transglutaminase (Acc. No. M55153), P37NB (slit homolog) (Acc. No. U32907), Serum amyloid A protein precursor (Acc. No. M26152), Alzheimer's disease amyloid A4 protein precursor (Acc. No. D87675), Complement C3 precursor (Acc. No. K02765), Testican (Acc. No. X73608), Integrin &bgr;3 (Acc. No. M35999), N-acetylgalactosamine-6-sulfate sulfatase (Acc. No. U06088), Acid alpha-glucosidase (Acc. No. X55079), Acid lipase A (cholesterol esterase) (Acc. No. X76488), Lysosomal pepstatin-insensitive protease (CLN2) (Acc. No. AF017456), Superoxide dismutase 2 (Acc. No. X07834), Metaxin (Acc. No. J03060), 2,4-dienoyl-CoA reductase (Acc. No. U78302), Ulbiquitin-conjugating enzyme (UbcH8) (Acc. No. AF031141), Ubiquitin-specific protease 8 (Acc. No. D29956), RTP/Cap43/Drg1/Ndr1(Inducible by nickel, retinoids, homocysteine and ER stress) (Acc. No. D87953), C-193 muscle ankyrin-repeat nuclear protein (cytokine-inducible) (Acc. No. X83703), LRP major vault protein associated with multidrug resistance (Acc. No. X79882), &bgr;-arrestin related HHCPA78 homolog (upregulated by vitamin D3) (Acc. No. S73591), R-RAS (Acc. No. M14949), RAB 13 small GTPase (Acc. No. X75593), P66 SHC (ski oncogene) (Acc. No. U73377), MK-STYX (MAP kinase phosphatase-like protein) (Acc. No. N75168), H73 nuclear antigen/MA-3 apoptosis-related/TIS (topoisomerase-inhibitor suppressed) (Acc. No. U96628), Natural killer cells protein 4 (Acc. No. M598071), TXK tyrosine kinase (T-cell specific) (Acc. No. L27071), X-linked PEST-containing transporter (Acc. No. U05321), AMP deaminase 2 (Acc. No. M91029), FIP2/HYPL huntingtin-interacting protein (Acc. No. AF061034), DNASE I homolog (Acc. No. X90392), Transcription factor 11 (Acc. No. X77366), Histone H2A.2 (Acc. No. L19779), Histone H2B (Acc. No. AL021807), 23808 (Acc. No. AF038192), CGI-147 (Acc. No. AA307912), EST (Acc. No. W89120), EST (Acc. NO. AI026140), EST (Acc. No. AA218982), or EST (Acc. No. W63684); and (c) identifying the compound as an inhibitor of p21-mediated modulation of cellular gene expression if expression of the cellular gene of subpart (b) is changed to a lesser extent in the present of the compound than in the absence of the compound.