The p56 -interacting Protein p62 Stimulates Transcription via the SV40 Enhancer (1999)

p62 is a recently identified ubiquitin-binding, cytosolic phosphoprotein that interacts with several signal transduction molecules including the tyrosine kinase p56lck and the protein kinase C-ζ. p62 is therefore suggested to serve an important role in signal transduction in the cell, although the physiological function of p62 remains undefined. Here we demonstrate by transient transfection assays that p62 stimulates the transcription of reporter genes linked to the simian virus 40 (SV40) enhancer. A putative p62-responsive element was localized to the B domain of the distal 72-base pair repeat of the SV40 enhancer. p62 was unable to bind this element in vitro, nor was it able to activate transcription when directly tethered to a promoter, suggesting that p62 stimulates transcription via an indirect mechanism. Stimulation of transcription mediated by p62 was dependent on its amino-terminal region, which is also necessary for interaction with cell surface signaling molecules. These findings indicate that p62 may link extracellular signals directly to transcriptional responses, and identify the SV40 enhancer as a downstream target for signal transduction pathways in which p62 participates. p62 is a recently identified ubiquitin-binding, cytosolic phosphoprotein that interacts with several signal transduction molecules including the tyrosine kinase p56lck and the protein kinase C-ζ. p62 is therefore suggested to serve an important role in signal transduction in the cell, although the physiological function of p62 remains undefined. Here we demonstrate by transient transfection assays that p62 stimulates the transcription of reporter genes linked to the simian virus 40 (SV40) enhancer. A putative p62-responsive element was localized to the B domain of the distal 72-base pair repeat of the SV40 enhancer. p62 was unable to bind this element in vitro, nor was it able to activate transcription when directly tethered to a promoter, suggesting that p62 stimulates transcription via an indirect mechanism. Stimulation of transcription mediated by p62 was dependent on its amino-terminal region, which is also necessary for interaction with cell surface signaling molecules. These findings indicate that p62 may link extracellular signals directly to transcriptional responses, and identify the SV40 enhancer as a downstream target for signal transduction pathways in which p62 participates. The putative signaling molecule p62 is a novel human phosphoprotein that was originally identified through its interaction with the Src homology domain 2 (SH2) 1The abbreviations used are: SH2, Src homology domain 2; ORCA, orphan receptor coactivator; bp, base pairs; CAT, chloramphenicol acetyltransferase; EMSA, electrophoretic mobility shift analysis; HA, hemagglutinin; PCR, polymerase chain reaction; PKC, protein kinase C; PPARα, peroxisome proliferator-activated receptor α; RXRα, 9-cis-retinoic acid receptor; SV40, simian virus 40; TK, thymidine kinase. of p56lck, a T-cell specific Src family tyrosine kinase required for T-cell signal transduction (1Joung I. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 5991-5995Crossref PubMed Scopus (156) Google Scholar, 2Park I. Chung J. Walsh C.T. Yun Y. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 12338-12342Crossref PubMed Scopus (89) Google Scholar). p62 was also cloned independently as a factor that binds to the orphan nuclear hormone receptor COUP-TFII, orphan nuclear receptor coactivator (ORCA) (3Marcus S.L. Winrow C.J. Capone J.P. Rachubinski R.A. J. Biol. Chem. 1996; 271: 27197-27200Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar), a rat protein that binds to the atypical protein kinase C (PKC)-ζ (ZIP or PKC-ζ-interacting protein) (4Puls A. Schmidt S. Grawe F. Stabel S. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 6191-6196Crossref PubMed Scopus (194) Google Scholar), as a murine gene (A170) induced by oxidative stress in macrophages (5Ishii T. Yanagawa T. Kawane T. Yuki K. Seita J. Yoshida H. Bannai S. Biochem. Biophys. Res. Commun. 1996; 226: 456-460Crossref PubMed Scopus (79) Google Scholar), and as a protein (EBIAP) that associates with a novel cytokine receptor induced in Epstein-Barr virus infected B-cells (6Devergne O. Hummel M. Koeppen H. LeBeau M.M. Nathanson E.C. Kieff E. Birkenbach M. J. Virol. 1996; 70: 1143-1153Crossref PubMed Google Scholar). p62 is a ubiquitously expressed cytosolic phosphoprotein encoded by an immediate-early response gene that is rapidly induced by a variety of extracellular signals known to stimulate cell proliferation, differentiation, and response to oxidative stress (7Lee Y.H. Ko J. Joung I. Kim J.H. Shin J. FEBS Lett. 1998; 438: 297-300Crossref PubMed Scopus (26) Google Scholar, 8Ishii T. Yanagawa T. Yuki K. Kawane T. Yoshida H. Bannai S. Biochem. Biophys. Res. Commun. 1997; 232: 33-37Crossref PubMed Scopus (56) Google Scholar). p62 binds to the SH2 domain of p56lck; however, interaction between the two proteins is atypical in that it is independent of phoshotyrosine (1Joung I. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 5991-5995Crossref PubMed Scopus (156) Google Scholar). The amino-terminal region of p62 contains determinants required for binding to the SH2 domain of p56lck, as well as for interaction with PKC-ζ and COUP-TFII (3Marcus S.L. Winrow C.J. Capone J.P. Rachubinski R.A. J. Biol. Chem. 1996; 271: 27197-27200Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 4Puls A. Schmidt S. Grawe F. Stabel S. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 6191-6196Crossref PubMed Scopus (194) Google Scholar). p62 can be phosphorylated in vitro by PKC-ζ, by a tightly associated Ser/Thr kinase, as well as by casein kinase II-like protein kinases (9Yanagawa T. Yuki K. Yoshida H. Bannai S. Ishii T. Biochem. Biophys. Res. Commun. 1997; 241: 157-163Crossref PubMed Scopus (19) Google Scholar). The association of p62 with signaling molecules such as p56lck and PKC-ζ, possibly with a Ras-GTPase activating protein (2Park I. Chung J. Walsh C.T. Yun Y. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 12338-12342Crossref PubMed Scopus (89) Google Scholar), as well as with other cellular factors, suggests that p62 plays diverse and important roles in cell surface signaling events, perhaps by serving as a tether or scaffold linking multiple and distinct signaling molecules. An important clue to the cellular function of p62 came with the recent demonstration that p62 is a multiubiquitin-binding protein (10Vadlamudi R.K. Joung I. Strominger J.L. Shin J. J. Biol. Chem. 1996; 271: 20235-20237Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar). Protein ubiquitination is a post-translational modification that primarily serves to target proteins for degradation via the 26 S proteosome. p62 does not appear to be associated with the proteosome, but may be part of a novel cytosolic structure that serves to sequester ubiquitinated proteins (11Shin J. Arch. Pharmacal Res. (Seoul). 1998; 21: 629-633Crossref PubMed Scopus (116) Google Scholar). p62 may therefore link signal transduction pathways to the regulation of ubiquitin-mediated protein degradation. We have previously demonstrated that p62 interacts with COUP-TFII, an orphan member of the nuclear hormone receptor superfamily of ligand-activated transcription factors (3Marcus S.L. Winrow C.J. Capone J.P. Rachubinski R.A. J. Biol. Chem. 1996; 271: 27197-27200Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). In transient transfection assays, co-transfection of p62 was shown to potentiate transactivation mediated by COUP-TFII, suggesting that p62 may directly participate in gene regulation. In this paper, we demonstrate that p62 stimulates transcription of reporter genes that are linked to the SV40 enhancer. Stimulation of transcription mediated by p62 was dependent on the amino-terminal region of p62, which is also necessary for interaction with cell surface signaling molecules. However, p62 was unable to bind to the SV40 enhancer or to stimulate transcription when directly tethered to DNA, suggesting that p62 functions indirectly. These findings indicate that p62 may link extracellular signals directly to transcriptional responses, and identify the SV40 enhancer as a downstream target for signal transduction pathways in which p62 participates. BSC40 and COS-1 cells were maintained in Dulbecco's modified Eagle's medium containing 10% (v/v) calf serum. Expression vectors for the mouse peroxisome proliferator-activated receptor α (PPARα), the human 9-cis-retinoic acid receptor (RXRα) (12Marcus S.L. Miyata K.S. Zhang B. Subramani S. Rachubinski R.A. Capone J.P. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 5723-5727Crossref PubMed Scopus (163) Google Scholar), and the luciferase reporter plasmid pSV2luc (13de Wet J.R. Wood K.V. DeLuca M. Helinski D.R. Subramani S. Mol. Cell. Biol. 1987; 7: 725-737Crossref PubMed Scopus (2481) Google Scholar) have been described elsewhere. The plasmid pCMVL containing the cytomegalovirus enhancer/promoter was a kind gift of Scott Bunnell (University of Alberta). The SV40 enhancer was amplified by the polymerase chain reaction (PCR) from pSV-SPORT (Life Technologies, Inc.) using the oligonucleotides 5′-ATTGGATCCGAATGTGTGTCAGTTAGC (forward primer) and 5′-ATTGGATCCTGGTTGCTGACTAATTGAGA (reverse primer). Two products resulted from this amplification, one of 160 base pairs (bp) and containing the entire SV40 enhancer, the other of 100 bp and containing the distal 72-bp repeat and 5′-flanking region. The products were digested with BamHI, gel purified, and inserted into theBglII site of the luciferase reporter vector, pGL2-promoter (Promega, Madison, WI). The resulting plasmids, pENH.FOR/GL2 and pENH.REV/GL2, contain the 160-bp insert in the forward and reverse orientation, respectively. pENH.MIN/GL2 contains the distal 72-bp repeat and 5′-flanking region in the forward orientation. A double-stranded oligonucleotide containing XhoI overhangs 5′-TCGAGGCAGAAGTATGCAAAGCATGCATCTCAATTAGTCAGAAC and encompassing the A domain of the SV40 enhancer (14Zenke M. Grundström T. Matthes H. Wintzerith M. Schatz C. Wildeman A. Chambon P. EMBO J. 1986; 5: 387-397Crossref PubMed Scopus (234) Google Scholar) was inserted into the XhoI site of the pGL2-promoter. The resulting plasmids, pA(x1)/GL2 and pA(x3)/GL2, contain 1 and 3 copies of the A domain, respectively. The B domain of the SV40 enhancer (14Zenke M. Grundström T. Matthes H. Wintzerith M. Schatz C. Wildeman A. Chambon P. EMBO J. 1986; 5: 387-397Crossref PubMed Scopus (234) Google Scholar) was amplified by PCR with the primer pairs 5′-ATTCTCGAGCAGCTGTGGAATGTG (forward) and 5′-ATTCTCGAGCTGGGGAGCCTGG (reverse). The product was digested withXhoI and inserted into the XhoI site of pGL2-promoter to generate pB(x1)/GL2 and pB(x2)/GL2, containing 1 and 2 copies of the B domain, respectively. The thymidine kinase (TK) promoter was amplified by PCR using the primer pairs 5′-ATTAGATCTCAAACCCCGCCCAGCG (forward) and 5′-ATTAAGCTTGATCTGCGGCACGCTG (reverse). The resulting product was digested with BglII and HindIII and inserted into the corresponding sites of the promoterless pGL2 luciferase vector (Promega). The 21-bp repeats of the SV40 early promoter were amplified by PCR using 5′-ATTAGATCTGCATCTCAATTAGTCAG (forward primer) and 5′-ATTAGATCTGGGGCGGAGAATGGGC (reverse primer). The product was digested with BglII and inserted into the BglII site of TKluc to generate pGC/TKluc. The entire natural SV40 enhancer was amplified by PCR using the primer pairs 5′-ATTCTCGAGCTGTGGAATGTGTGTCAG (forward) and 5′-ATTCTCGAGTGGTTGCTGACTAATTGAG (reverse). The product was digested with XhoI and inserted into the XhoI site of TKluc to generate pENH/TKluc. Construction of the expression vector pORCA/SG5 and derivatives pORCAΔ128–163 and pORCAΔ258–440 have been described (3Marcus S.L. Winrow C.J. Capone J.P. Rachubinski R.A. J. Biol. Chem. 1996; 271: 27197-27200Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). pORCAΔ1–187 was constructed as follows: an EcoRI site by an was inserted of by using the primer and from The resulting plasmid was digested with and the corresponding to acid was inserted into the EcoRI site of The acid of p62 were by using and from pORCA/SG5 to generate was constructed using was by in The reporter plasmid which contains copies of the site of the chloramphenicol and the expression plasmid which contains the domain to the domain of have been described B. P. P. M. Capone J.P. 1995; PubMed Scopus Google Scholar). p62 as an with the was constructed by an EcoRI containing the for p62 into the EcoRI site of B. P. P. M. Capone J.P. 1995; PubMed Scopus Google Scholar). BSC40 or COS-1 cells were 3 were by the as described B. S.L. K. Subramani S. Rachubinski R.A. Capone J.P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar), by a of a luciferase reporter gene of the p62 expression plasmid was by of was with were and luciferase was as described previously B. S.L. K. Subramani S. Rachubinski R.A. Capone J.P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). with cells were as using of reporter gene and 2 of or of was as described previously B. P. P. M. Capone J.P. 1995; PubMed Scopus Google Scholar). The of p62 was to a for by a BglII site by using the oligonucleotide and pORCA/SG5 A with BglII the which contains two repeats of the acid virus R.A. PubMed Scopus Google Scholar), was into the BglII site the p62 to generate was from COS-1 cells by using a was by was to K. in Scholar). of was were by with an to mouse and human were in by of protein expressed in The which the acid was from the Protein from cells were in Protein was with a using as a of protein was to on a 10% as described K. in Scholar). were to for were by were from COS-1 cells with pORCA/SG5 or with vector, and was as described previously B. S.L. K. Subramani S. Rachubinski R.A. Capone J.P. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). were for protein The entire SV40 enhancer 21-bp repeats was amplified by PCR using 5′-ATTGGATCCGAATGTGTGTCAGTTAGC (forward primer) and (reverse primer). The resulting product was digested with and with and the of polymerase I. were by on with 1 acid as p62 was in E. as a to kind gift of of Alberta). The protein was from on and the was with to the We originally cloned using the with the nuclear hormone receptor COUP-TFII as (3Marcus S.L. Winrow C.J. Capone J.P. Rachubinski R.A. J. Biol. Chem. 1996; 271: 27197-27200Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). In of the function of p62, we that the of reporter genes linked to the SV40 promoter was in transient transfection assays in the of an expression vector for suggested that p62 be in transcription this we BSC40 cells with the luciferase reporter plasmid which contains the SV40 promoter, in the or of the p62 expression shown in co-transfection of pORCA/SG5 resulted in a of luciferase as with with expression in was specific for the SV40 promoter, as co-transfection of pORCA/SG5 with a luciferase reporter containing the cytomegalovirus enhancer/promoter or the SV40 promoter not in of luciferase the of a reporter plasmid of the virus promoter was by of p62 not These findings indicate that of gene expression was dependent the of the SV40 enhancer region. of reporter gene was to an in we and of this we used an expression plasmid containing the SV40 promoter linked to for nuclear hormone The were into COS-1 cells in the or of which p62 its with the to of the expression of p62 in were and into two was from one and to with Protein were from the other and to with specific shown in for the nuclear hormone and were in the of and as with with vector 2 to 3 for and to for The in with an in the of the corresponding and proteins and 2 to 3 for and for The of in cells with was by with to The findings indicate that of reporter gene with of The SV40 early promoter of copies of a 21-bp by a (14Zenke M. Grundström T. Matthes H. Wintzerith M. Schatz C. Wildeman A. Chambon P. EMBO J. 1986; 5: 387-397Crossref PubMed Scopus (234) Google Scholar, S. Cell. 1986; Full Text PDF PubMed Scopus Google Scholar, Biol. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, J. Cell. 1986; Full Text PDF PubMed Scopus Google Scholar, J.H. I. Matthes H. Chambon P. Cell. Full Text PDF PubMed Scopus Google Scholar). repeat two copies of a that been shown to bind the transcription factor The SV40 enhancer, from SV40 contains two copies of a 72-bp The enhancer been localized to the distal 72-bp repeat and 5′-flanking region (14Zenke M. Grundström T. Matthes H. Wintzerith M. Schatz C. Wildeman A. Chambon P. EMBO J. 1986; 5: 387-397Crossref PubMed Scopus (234) Google Scholar). the putative p62-responsive of the SV40 promoter, we several on the plasmid which contains a luciferase reporter gene linked to the SV40 early promoter of this plasmid in the of p62 expression plasmid resulted in in luciferase In the natural SV40 enhancer copies of the 72-bp in the forward or reverse resulted in a in luciferase A reporter plasmid that the distal 72-bp repeat and 5′-flanking region also luciferase in the of p62, although the of was natural SV40 enhancer. the SV40 early promoter, and in the 21-bp participate in we used a luciferase reporter linked to the of the or the 3 repeats of the SV40 early promoter of the with p62 expression plasmid not in a in luciferase with the reporter genes However, linking the natural SV40 enhancer directly to TKluc resulted in a in luciferase indicate that the distal 72-bp repeat of the SV40 enhancer is to p62 and that is independent of the 21-bp repeats or the SV40 Full function of the SV40 enhancer been shown to on the of multiple and which bind a variety of and Biol. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, J.H. I. Matthes H. Chambon P. Cell. Full Text PDF PubMed Scopus Google Scholar). The SV40 enhancer bp, including the distal 72-bp repeat and its 5′-flanking region (14Zenke M. Grundström T. Matthes H. Wintzerith M. Schatz C. Wildeman A. Chambon P. EMBO J. 1986; 5: 387-397Crossref PubMed Scopus (234) Google Scholar), and is of two distinct A and B. The A and B but can to activate can be by of the of the A and B to the of p62 on the SV40 enhancer, we luciferase reporter gene containing or multiple copies of the A or B domain linked to the SV40 early by p62 via a B domain was but was when the B domain was In the of a reporter gene containing a or 3 copies of the A domain was or by the B domain of the distal 72-bp repeat is necessary and to to to the by which p62 potentiate transcription via the SV40 enhancer, we using a containing the natural SV40 enhancer and 21-bp repeats to p62 binds to this element in The was with from COS-1 cells with pORCA/SG5 or the corresponding vector, The of the on this element with COS-1 cell not in the of p62 p62 not bind to the a to on this element were not or when p62 was with of COS-1 cell to the of p62 does not appear to be of binding directly or to the SV40 enhancer, or of the interaction of cellular factors with this p62 transcription activating we the plasmid linking the for p62 to the domain of the and transient transfection assays with a reporter gene copies of the site shown in the of this reporter gene was by the as However, when directly to DNA, was unable to stimulate transcription of the reporter gene p62 does not an and this with from the binding assays, suggests that p62 stimulates transcription through an indirect p62 contains a region its that homology to and a putative protein binding a that to be in a that may be a target for protein and a region its that is required for binding to to human (1Joung I. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 5991-5995Crossref PubMed Scopus (156) Google A. Schmidt S. Grawe F. Stabel S. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 6191-6196Crossref PubMed Scopus (194) Google Scholar, R.K. Joung I. Strominger J.L. Shin J. J. Biol. Chem. 1996; 271: 20235-20237Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar). The amino-terminal domain been shown to be required for interaction with p56lck, PKC-ζ, and identify of p62 that are important for the transcriptional of the SV40 enhancer, we a of derivatives of p62 and for in transient transfection A of p62 acid the to stimulate transcription of with with the protein the region and the domain, which several kinase are not for of transcription of the SV40 enhancer. a the putative interaction region However, derivatives the or were is the homology region this region, derivatives of p62 were constructed or shown in transcription of pSV2luc and as as the In was are for The homology region may also be however, in the of amino-terminal this region is for shown that of p62 are necessary for interaction with the domain (12Marcus S.L. Miyata K.S. Zhang B. Subramani S. Rachubinski R.A. Capone J.P. Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 5723-5727Crossref PubMed Scopus (163) Google Scholar). indicate that part of the domain of p62 is also for transactivation of the SV40 enhancer. p62 been shown to bind to a variety of cellular factors including signaling molecules such as p56lck, PKC-ζ, and cytokine the transcription factor and These with recent that p62 is expressed in cell and is rapidly induced by cell and that p62 is a protein that serves a role in signal transduction in the cell, perhaps linked to the regulation of ubiquitin-mediated protein degradation. However, the cellular of p62 remains a role for p62 in signal transduction regulation of protein degradation not been The findings that p62 also stimulates transcription via the SV40 enhancer, a to this protein and that p62 a link between cell surface signaling and specific gene mediated by p62 to be specific for the SV40 enhancer, the of other were by the of The natural SV40 enhancer copies of the 72-bp was the to p62 and when to the SV40 early promoter or to a we localized a putative p62-responsive element to the B domain of the 72-bp repeat of the SV40 enhancer. A of the B domain was to to however, the of was when the B domain was as is the with the natural enhancer. These that of multiple factors participate in p62 The by which p62 SV40 transcription is p62 does not bind to the SV40 enhancer on its or in with cellular factors, nor does it appear to the of cellular factors that with this p62 does not activate transcription when tethered directly to a p62 functions in perhaps as a transcription p62 a region of homology with the transcriptional coactivator of p62 and of suggesting in of region is part of a domain in that been shown to bind J.R. J.P. PubMed Scopus Google Scholar). However, this region of homology is not for transactivation of the SV40 enhancer by p62 is of p62 in the as one may it a role in transcription remains that the of p62 may be in the of the of the rat of p62, is in the of PKC-ζ (4Puls A. Schmidt S. Grawe F. Stabel S. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 6191-6196Crossref PubMed Scopus (194) Google Scholar). An is that p62 the function of cellular transcription factors that target the SV40 enhancer. p62 been shown to have a tightly or Ser/Thr protein kinase (1Joung I. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 5991-5995Crossref PubMed Scopus (156) Google Scholar, 2Park I. Chung J. Walsh C.T. Yun Y. Strominger J.L. Shin J. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 12338-12342Crossref PubMed Scopus (89) Google Scholar). p62 may activate one or SV40 transcription factors directly or by part of the and domain of p62 is also required for p62 may link cell surface signaling pathways to transcription factor The SV40 enhancer contains multiple binding sites for a of and transcription factors, including transcription enhancer factor 1 J.H. I. Matthes H. Chambon P. Cell. Full Text PDF PubMed Scopus Google Scholar), transcription enhancer factor 2 I. M. M. A. Chambon P. 1987; PubMed Scopus Google Scholar), P. Cell. 1987; Full Text PDF PubMed Scopus Google Scholar), binding transcription factors M. M. I. Chambon P. EMBO J. 1987; PubMed Scopus Google Scholar), and M. C. A. F. I. Chambon P. EMBO J. PubMed Scopus Google Scholar, M. I. M. M. C. Chambon P. EMBO J. PubMed Scopus Google Scholar, Cell. 1986; Full Text PDF PubMed Scopus Google Scholar). is that and may response of the SV40 enhancer to P. Cell. 1987; Full Text PDF PubMed Scopus Google Scholar, and several other transcription factors that bind to this element are to by extracellular role factors in transcriptional is and through protein and transfection be that of the transcription factors that with the SV40 enhancer are not specific to this element and and important roles in cellular gene regulation PubMed Scopus Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, Mol. 1997; PubMed Scopus Google Scholar). it is that p62 a role as a of gene p62 also to the of transcription be with p62 a protein that may be in the regulation of ubiquitin-mediated protein degradation (10Vadlamudi R.K. Joung I. Strominger J.L. Shin J. J. Biol. Chem. 1996; 271: 20235-20237Abstract Full Text Full Text PDF PubMed Scopus (258) Google Scholar). is for that p62 may target transcriptional that bind to the SV40 enhancer for degradation. is a of of transcription factors is by degradation F. F. 1996; PubMed Scopus Google Scholar). However, such a an for the region of p62 that is required for binding is in for its In we have demonstrated that p62, a protein known to with distinct of the cell surface signal transduction is able to activate We have identified a of the SV40 enhancer as one of its downstream that a region of p62 that is necessary for its interaction with cellular signaling molecules is also required for its to stimulate p62 in linking cell surface signal transduction pathways to transcriptional We for the expression