Key points are not available for this paper at this time.
SRC1, initially identified as a nuclear receptor coactivator, was found to interact with a member of the transcriptional enhancer factor (TEF) family of transcription factors, TEF-4. The interaction, which occurs in both intact cells and in a cell-free system, is mediated by the highly conserved basichelix-loop-helix/Per-Arnt-Sim (bHLH-PAS) domain present in the N-terminal region of SRC1. Moreover, all three members of the p160 family of nuclear receptor coactivators, SRC1, TIF2, and RAC3, are able to potentiate transcription from a TEF response element in transient transfection experiments, and this activation requires the presence of the bHLH-PAS domain. These results suggest that the p160 proteins could be bona fidecoactivators of the TEF family of transcription factors. SRC1, initially identified as a nuclear receptor coactivator, was found to interact with a member of the transcriptional enhancer factor (TEF) family of transcription factors, TEF-4. The interaction, which occurs in both intact cells and in a cell-free system, is mediated by the highly conserved basichelix-loop-helix/Per-Arnt-Sim (bHLH-PAS) domain present in the N-terminal region of SRC1. Moreover, all three members of the p160 family of nuclear receptor coactivators, SRC1, TIF2, and RAC3, are able to potentiate transcription from a TEF response element in transient transfection experiments, and this activation requires the presence of the bHLH-PAS domain. These results suggest that the p160 proteins could be bona fidecoactivators of the TEF family of transcription factors. steroid receptor coactivator nuclear receptor basichelix-loop-helix/Per-Arnt-Sim transcriptional enhancer factor polymerase chain reaction glutathione S-transferase 17β-estradiol Transcriptional coactivators, recruited by sequence-specific transcription factors, enhance transcriptional activation of target genes via interactions with chromatin remodeling complexes and components of the basal transcriptional apparatus (1Peterson C.L. Logie C. J. Cell. Biochem. 2000; 78: 179-185Crossref PubMed Scopus (67) Google Scholar, 2Kingston R.E. Narlikar G.J. Genes Dev. 1999; 13: 2339-2352Crossref PubMed Scopus (609) Google Scholar). Three related 160-kDa proteins, SRC1, TIF2, and RAC3, encoded by separate genes, form the steroid receptor coactivator (SRC)1 or p160 family of coactivators (for a review, see Refs. 3McKenna N.J. Lanz R.B. O'Malley B.W. Endocr. Rev. 1999; 20: 321-344Crossref PubMed Scopus (1658) Google Scholar and 4Glass C.K. Rosenfeld M.G. Genes Dev. 2000; 14: 121-141Crossref PubMed Google Scholar). These proteins are highly homologous and were initially identified as factors that interacted with nuclear receptors (NRs) in the presence of ligand and were able to enhance receptor-dependent transcriptional activation (5Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2063) Google Scholar, 6Voegel J.J. Heine M.J. Zechel C. Chambon P. Gronemeyer H. EMBO J. 1996; 15: 3667-3675Crossref PubMed Scopus (953) Google Scholar, 7Li H. Gomes P.J. Chen J.D. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 8479-8484Crossref PubMed Scopus (504) Google Scholar). The p160 proteins have been reported to potentiate the activity not only of NRs but also a number of other transcription factors (8Na S.Y. Lee S.K. Han S.J. Choi H.S. Im S.Y. Lee J.W. J. Biol. Chem. 1998; 273: 10831-10834Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar, 9Lee S.K. Kim H.J. Na S.Y. Kim T.S. Choi H.S. Im S.Y. Lee J.W. J. Biol. Chem. 1998; 273: 16651-16654Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar, 10Kim H.J. Kim J.H. Lee J.W. J. Biol. Chem. 1998; 273: 28564-28567Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 11Yanagisawa J. Yanagi Y. Masuhiro Y. Suzawa M. Watanabe M. Kashiwagi K. Toriyabe T. Kawabata M. Miyazono K. Kato S. Science. 1999; 283: 1317-1321Crossref PubMed Scopus (420) Google Scholar, 12Lee S.K. Kim H.J. Kim J.W. Lee J.W. Mol. Endocrinol. 1999; 13: 1924-1933Crossref PubMed Scopus (68) Google Scholar, 13Carrero P. Okamoto K. Coumailleau P. O'Brien S. Tanaka H. Poellinger L. Mol. Cell. Biol. 2000; 20: 402-415Crossref PubMed Scopus (327) Google Scholar, 14Chen S.L. Dowhan D.H. Hosking B.M. Muscat G.E. Genes Dev. 2000; 14: 1209-1228Crossref PubMed Google Scholar), although the mechanisms by which the p160s enhance the activity of other signaling pathways are less well characterized. The p160 proteins contain conserved domains responsible for the interaction with NRs (15Heery D.M. Kalkhoven E. Hoare S. Parker M.G. Nature. 1997; 387: 733-736Crossref PubMed Scopus (1778) Google Scholar, 16Torchia J. Rose D.W. Inostroza J. Kamei Y. Westin S. Glass C.K. Rosenfeld M.G. Nature. 1997; 387: 677-684Crossref PubMed Scopus (1108) Google Scholar), and protein interaction domains responsible for the recruitment of downstream effectors, such as histone acetyltransferases like CBP/p300 (17Bannister A.J. Kouzarides T. Nature. 1996; 384: 641-643Crossref PubMed Scopus (1535) Google Scholar, 18Ogryzko V.V. Schiltz R.L. Russanova V. Howard B.H. Nakatani Y. Cell. 1996; 87: 953-959Abstract Full Text Full Text PDF PubMed Scopus (2409) Google Scholar) and protein methyltransferases (19Chen D. Ma H. Hong H. Koh S.S. Huang S.M. Schurter B.T. Aswad D.W. Stallcup M.R. Science. 1999; 284: 2174-2177Crossref PubMed Scopus (1006) Google Scholar). In addition, the p160 coactivators have a highly conserved N-terminal basichelix-loop-helix/Per-Arnt-Sim (bHLH-PAS) domain. The bHLH domain is a DNA binding and protein dimerization motif shared by many transcription factors (20Murre C. McCaw P.S. Baltimore D. Cell. 1989; 56: 777-783Abstract Full Text PDF PubMed Scopus (1863) Google Scholar), and in the bHLH-PAS subfamily an additional dimerization motif, called PAS domain, extends from the C-terminal end of the HLH domain (21Crews S.T. Fan C.M. Curr. Opin. Genet. Dev. 1999; 9: 580-587Crossref PubMed Scopus (161) Google Scholar). The bHLH-PAS domain present in the p160 proteins has a striking homology with those from the bHLH-PAS family of transcription factors, and it is also the most conserved region between the three members of the family. Nevertheless, its function remains unclear and it seems to be dispensable for the enhancing of the NR transcriptional activity in cotransfection studies (5Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Science. 1995; 270: 1354-1357Crossref PubMed Scopus (2063) Google Scholar). Therefore, the role of this putative protein dimerization motif in the stabilization of competent coactivator complexes, mediating accessory protein-protein interactions and/or the recruitment of p160 coactivators by other transcription factors remains to be established. To understand the molecular mechanisms of SRC1 functions and identify its associated proteins, we performed a yeast two-hybrid screen using the bHLH-PAS domain of SRC1 as bait. In this report we present evidence supporting a role for the p160 proteins as coactivators for the transcriptional enhancer factor (TEF) family of transcription factors (22Jacquemin P. Hwang J.J. Martial J.A. Dolle P. Davidson I. J. Biol. Chem. 1996; 271: 21775-21785Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar), which are implicated in the regulation of many developmental processes, such as the control of cardiac and skeletal muscle-specific gene expression (23Farrance I.K. Mar J.H. Ordahl C.P. J. Biol. Chem. 1992; 267: 17234-17240Abstract Full Text PDF PubMed Google Scholar, 24Kariya K. Farrance I.K. Simpson P.C. J. Biol. Chem. 1993; 268: 26658-26662Abstract Full Text PDF PubMed Google Scholar, 25Stewart A.F. Larkin S.B. Farrance I.K. Mar J.H. Hall D.E. Ordahl C.P. J. Biol. Chem. 1994; 269: 3147-3150Abstract Full Text PDF PubMed Google Scholar, 26Carson J.A. Schwartz R.J. Booth F.W. Am. J. Physiol. 1996; 270: C1624-C1633Crossref PubMed Google Scholar), early gene expression in mouse development (27Melin F. Miranda M. Montreau N. DePamphilis M.L. Blangy D. EMBO J. 1993; 12: 4657-4666Crossref PubMed Scopus (45) Google Scholar), and human chorionic somatomammotropin (hCS) gene expression in the placenta (28Jacquemin P. Martial J.A. Davidson I. J. Biol. Chem. 1997; 272: 12928-12937Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 29Jiang S.W. Wu K. Eberhardt N.L. Mol. Endocrinol. 1999; 13: 879-889Crossref PubMed Google Scholar). A region of SRC1 encoding the bHLH-PAS domain (amino acids 1–361) was cloned in frame 3′ of the DNA binding domain of LexA in pBTM116 to generate a bait fusion protein. A mouse embryo (9.5–12.5 dpc) cDNA library in the pASV3 vector (30Le Douarin B. Pierrat B. vom Baur E. Chambon P. Losson R. Nucleic Acids Res. 1995; 23: 876-878Crossref PubMed Scopus (71) Google Scholar) was used for screening according to the modified protocols described by Hollenberg et al. (31Hollenberg S.M. Sternglanz R. Cheng P.F. Weintraub H. Mol. Cell. Biol. 1995; 15: 3813-3822Crossref PubMed Scopus (585) Google Scholar). The bait and the library were sequentially transformed into Saccharomyces cerevisiaestrain L40a using the lithium acetate method. Polypeptides interacting with SRC1 bHLH-PAS domain were detected by the ability to activate transcription of HIS3 and lacZ reporter genes. Colonies able to grow on HIS-deficient medium containing 40 mm 3-amino-1,2,4-triazole were selected and tested for β-galactosidase expression. pASV3 plasmids from His+, LacZ+ colonies were isolated, and cDNA inserts were determined by automated sequencing. The first 528 nucleotides of the partial TEF-4 clone 1.6 were amplified by PCR and32P-labeled using the Multiprime DNA Labeling System (Amersham Pharmacia Biotech). This probe was used to screen a high density DNA Filter containing a mouse embryo (9 dpc) cDNA library using the protocols provided by the manufacturer (Resource Center/Primary Data Base, Max Planck Institute for Molecular Genetics, Heubnerweg 6, Berlin, Germany). The clone MPMGp559M1368Q2 encodes the full-length cDNA of mouse TEF-4, identical to the TEF-4 in the data bases (GenBankTM accession number D50563). The following plasmids have been described previously; pSG5-SRC1e (32Kalkhoven E. Valentine J.E. Heery D.M. Parker M.G. EMBO J. 1998; 17: 232-243Crossref PubMed Scopus (275) Google Scholar), pSG5-SRC1eΔAD1 (33Bevan C.L. Hoare S. Claessens F. Heery D.M. Parker M.G. Mol. Cell. Biol. 1999; 19: 8383-8392Crossref PubMed Scopus (334) Google Scholar), pSG5-TIF2 (6Voegel J.J. Heine M.J. Zechel C. Chambon P. Gronemeyer H. EMBO J. 1996; 15: 3667-3675Crossref PubMed Scopus (953) Google Scholar), pCMX.F.RAC3 (7Li H. Gomes P.J. Chen J.D. Proc. Natl. Acad. Sci. U. S. A. 1997; 94: 8479-8484Crossref PubMed Scopus (504) Google Scholar), pXJ40-TEF-1A (34Xiao J.H. Davidson I. Matthes H. Garnier J.M. Chambon P. Cell. 1991; 65: 551-568Abstract Full Text PDF PubMed Scopus (304) Google Scholar), and pMT2-MOR (35Lahooti H. White R. Hoare S.A. Rahman D. Pappin D.J. Parker M.G. J. Steroid Biochem. Mol. Biol. 1995; 55: 305-313Crossref PubMed Scopus (33) Google Scholar). pSG5-ΔPAS-SRC1e was created by insertion of the fragment SRC1e-(381–1399) into the XbaI and BglII sites of pSG5 (MCS) (32Kalkhoven E. Valentine J.E. Heery D.M. Parker M.G. EMBO J. 1998; 17: 232-243Crossref PubMed Scopus (275) Google Scholar). The partial TEF-4 clone 1.6 and the complete open reading frame of the full-length TEF-4 were amplified by PCR and cloned into the EcoRI and XhoI sites of pSG5. GST-SRC1-(1–807) was created by insertion of the relevant fragment into the BglII and SalI sites of pGEX-4T-3 (Amersham Pharmacia Biotech). The first 450 amino acids of SRC1 were inserted into the BamHI and EcoRI sites of pGEX-2TK (Amersham Pharmacia Biotech) to generate the GST-SRC1-(1–450) vector. The pRL-EF-1α control reporter vector was created by insertion of the Polypeptide chain elongation factor 1α promoter, amplified using the pEF-BOS vector as template (36Mizushima S. Nagata S. Nucleic Acids Res. 1990; 18: 5322Crossref PubMed Scopus (1499) Google Scholar), into theBglII and HindIII sites of the pRL-null vector (Promega). The pGL3-MCAT/SV40 luciferase reporter was created by amplifying the multimerized TEF response element present in the M-CAT/SV40cat vector (37Larkin S.B. Farrance I.K. Ordahl C.P. Mol. Cell. Biol. 1996; 16: 3742-3755Crossref PubMed Scopus (72) Google Scholar) and subsequent subcloning into theSacI and NheI sites of pGL3-basic vector (Promega). The pGL3–2XERE-PS2 luciferase reporter was created by insertion of the 2XERE-PS2 sequence, amplified using the vector 2XERE-PS2-CAT (38Montano M.M. Kraus W.L. Katzenellenbogen B.S. Mol. Endocrinol. 1997; 11: 330-341Crossref PubMed Scopus (17) Google Scholar) as template, into the KpnI andNcoI sites of pGL3-basic vector. All constructs created by PCR amplification with Elongase enzyme mix (Life Technologies, Inc.) were verified by sequencing. Recombinant cDNAs in the pSG5 expression vector were transcribed and translated in vitroin the presence of 35Smethionine in reticulocyte lysate (Promega) according to the manufacturer's protocol. GST fusion proteins were induced, purified, bound to Sepharose beads (Amersham Pharmacia Biotech), and incubated with translated proteins as described previously (32Kalkhoven E. Valentine J.E. Heery D.M. Parker M.G. EMBO J. 1998; 17: 232-243Crossref PubMed Scopus (275) Google Scholar) in NETN buffer (20 mm Tris-HCl (pH 8.0), 1 mm EDTA, 0.5 Nonidet P-40, 100 mm NaCl). After extensive washing, the samples were separated on SDS-10% polyacrylamide gels. Gels were fixed and dried, and the35S-labeled proteins were visualized by fluorography. COS-1 and HeLa cells were routinely maintained in E4 supplemented with 10% fetal bovine serum. Twenty-four hours before transfection, HeLa cells were plated in 96-well microtitrer plates in phenol red-free medium supplemented with 5% fetal bovine serum (dextran charcoal-stripped serum when using E2 in the assay). Transfection was performed by a modified calcium phosphate (39Chen C. Okayama H. Mol. Cell. Biol. 1987; 7: 2745-2752Crossref PubMed Scopus (4824) Google Scholar). The transfected DNA included a pRL-EF-1α control plasmid (0.1 ng), pGL3-MCAT/SV40-luc (20 ng), or pGL3–2XERE-PS2-Luc (10 ng) reporters and either pMT2-MOR (2.5 ng) cotransfected with 10 ng of pSG5-SRC1 or pSG5-ΔPAS-SRC1e or 30 ng of expression vector encoding the wild or of the p160s as in the to were used to the of After for the cells were and incubated in medium for reporter The reporter luciferase activity was using the luciferase activity used as control was determined by the of mm and to the luciferase The luciferase activity was used to for in transfection the and were in COS-1 cells using as described (32Kalkhoven E. Valentine J.E. Heery D.M. Parker M.G. EMBO J. 1998; 17: 232-243Crossref PubMed Scopus (275) Google Scholar). from COS-1 cells or were separated on and The were in (20 mm Tris-HCl (pH mm containing 5% with and incubated for 1 with SRC1 mouse SRC1 After the were incubated with and with The bound were visualized using the (Amersham Pharmacia Biotech). used a yeast two-hybrid to identify mouse cDNAs encoding proteins that interact with the N-terminal region of SRC1, the highly conserved bHLH-PAS domain (amino acids 1 containing the to the bHLH-PAS domain, and mouse proteins to the activation domain were selected according to ability to grow in a medium The were identified and tested for β-galactosidase that clone encoded a TEF-4 with the N-terminal region (amino acids to the C-terminal region (amino acids when with the M. K. T. T. H. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus (61) Google Scholar) 1 To the of the interaction, the plasmid the TEF-4 to the or the were into yeast the to the bHLH-PAS domain or the The interactions were by the of lacZ reporter expression in yeast using β-galactosidase 1 found a activity a interaction between the bHLH-PAS domain and the but the presence of the TEF-4 this activity that the N-terminal region of and the TEF-4 clone 1.6 are able to The encoded by the clone 1.6 the N-terminal of TEF-4 (amino acids and also has an of the region This the that the TEF-4 To this we a mouse embryo cDNA library with the partial TEF-4 clone as a probe and found encoding partial or full-length TEF-4. in all the cDNA were identical to that described that the in interaction between SRC1 and TEF-4 that we in yeast was also in using GST The TEF-4 encoded by the clone 1.6 bound to the N-terminal region of to GST in with the in interaction between SRC1 and the clone This in interaction was in using the bHLH-PAS domain and the full-length TEF-4 and we found that were able to interact member of the TEF family of transcription factors, (34Xiao J.H. Davidson I. Matthes H. Garnier J.M. Chambon P. Cell. 1991; 65: 551-568Abstract Full Text PDF PubMed Scopus (304) Google Scholar), also was able to to SRC1 in the that the interaction is not to a member of the TEF family. SRC1, TIF2, and are well coactivators that are recruited to the ligand enhancing transcriptional activity N.J. Lanz R.B. O'Malley B.W. Endocr. Rev. 1999; 20: 321-344Crossref PubMed Scopus (1658) Google Scholar, 4Glass C.K. Rosenfeld M.G. Genes Dev. 2000; 14: 121-141Crossref PubMed Google Scholar). a interaction between TEF transcription factors and SRC1 both in and in we SRC1 was able to potentiate transcriptional activation from a TEF response element in transfected the luciferase reporter plasmid pGL3-MCAT/SV40 (37Larkin S.B. Farrance I.K. Ordahl C.P. Mol. Cell. Biol. 1996; 16: 3742-3755Crossref PubMed Scopus (72) Google Scholar) we found that the expression of full-length of the luciferase reporter we cotransfected a the bHLH-PAS domain, the ability of to activate the transcription from the TEF response element was This of activation be by a expression of the SRC1 as of transfected using an that the SRC1 is Moreover, this SRC1 is able to potentiate the transcriptional activity mediated by the receptor in a transient transfection using the 2XERE-PS2 luciferase reporter that the is able to to the and interact with its downstream the the TEF binding was used in the transient transfection SRC1 activation of the luciferase reporter gene that the was of the in the TEF of either full-length TEF-4 or the activity of the TEF response element as has been reported previously in a of (34Xiao J.H. Davidson I. Matthes H. Garnier J.M. Chambon P. Cell. 1991; 65: 551-568Abstract Full Text PDF PubMed Scopus (304) Google Scholar, T. M.J. S. J.H. Davidson I. Chambon P. EMBO J. 1992; 11: PubMed Scopus Google Scholar, J.J. Chambon P. Davidson I. EMBO J. 1993; 12: PubMed Scopus Google Scholar, S.W. Eberhardt N.L. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar), and this was not by the cotransfection of SRC1 not SRC1 activation and (6Voegel J.J. Heine M.J. Zechel C. Chambon P. Gronemeyer H. EMBO J. 1996; 15: 3667-3675Crossref PubMed Scopus (953) Google Scholar, E. Valentine J.E. Heery D.M. Parker M.G. EMBO J. 1998; 17: 232-243Crossref PubMed Scopus (275) Google Scholar) 1 has been to the coactivator and this domain is for the transcriptional activation by the NRs (6Voegel J.J. Heine M.J. Zechel C. Chambon P. Gronemeyer H. EMBO J. 1996; 15: 3667-3675Crossref PubMed Scopus (953) Google Scholar, E. Valentine J.E. Heery D.M. Parker M.G. EMBO J. 1998; 17: 232-243Crossref PubMed Scopus (275) Google Scholar, C.L. Hoare S. Claessens F. Heery D.M. Parker M.G. Mol. Cell. Biol. 1999; 19: 8383-8392Crossref PubMed Scopus (334) Google Scholar). To was also for the of the TEF promoter, we cotransfected an expression vector encoding a with an of that region that not SRC1 from TEF response element The other members of the p160 and RAC3, were also able to potentiate the pGL3-MCAT/SV40 reporter in the transient transfection and this activation was that with SRC1 The TEF family of transcription factors is by a conserved DNA binding domain, Cell. 1991; Full Text PDF PubMed Scopus Google Scholar), which like and (23Farrance I.K. Mar J.H. Ordahl C.P. J. Biol. Chem. 1992; 267: 17234-17240Abstract Full Text PDF PubMed Google Scholar). The of to be and to interactions with proteins have been to interact with TEF proteins and enhance transcriptional the bHLH protein Max M. N. R. Mol. Cell. Biol. 1997; 17: PubMed Google Scholar), the protein S. Curr. Biol. 1999; 9: Full Text Full Text PDF PubMed Scopus Google Scholar), the human homologous P. R. Davidson I. J. A. 1999; PubMed Google Scholar), and the protein A.J. Ordahl C.P. Mol. Cell. Biol. 1999; 19: PubMed Scopus Google Scholar). In this report we that a member of the p160 family of transcriptional coactivators, SRC1, is able to interact and in with a TEF transcription TEF-4, using the bHLH-PAS protein dimerization motif present in its N-terminal Moreover, SRC1 is able to enhance the transcriptional activation from a TEF response element in transient transfection experiments, and this activation requires the presence of the bHLH-PAS domain. that this activation the interaction of SRC1 with TEF proteins present in the HeLa TEF transcription factor was also able to to the bHLH-PAS domain, a role of SRC1 as a coactivator for members of the TEF family. This has been on the that SRC1 is able to enhance in transient transfection the promoter, which TEF binding sites M. A. A. T. T. Mol. Cell. Endocrinol. 1999; PubMed Scopus Google Scholar). and were also able to potentiate the TEF response that the highly conserved bHLH-PAS domain a role for all the p160 proteins in the recruitment of coactivators to the TEF family of transcription factors. The when TEF proteins were was not by cotransfected SRC1, that other factors the p160 coactivators are also for TEF transcriptional interaction between TEF proteins and the protein could that as has been reported for S.W. Eberhardt N.L. J. Biol. Chem. 1996; 271: Full Text Full Text PDF PubMed Scopus Google Scholar). The SRC1 bHLH-PAS domain is for enhancing the TEF in it is dispensable for of transcription by In the of the response element the was an coactivator the full-length protein. This could be in of for a of coactivators, shared between the which interact with the p160 proteins via (15Heery D.M. Kalkhoven E. Hoare S. Parker M.G. Nature. 1997; 387: 733-736Crossref PubMed Scopus (1778) Google Scholar, 16Torchia J. Rose D.W. Inostroza J. Kamei Y. Westin S. Glass C.K. Rosenfeld M.G. Nature. 1997; 387: 677-684Crossref PubMed Scopus (1108) Google Scholar) and other transcription factors that the p160 coactivators via the bHLH-PAS it has been that the homologous of TIF2, its bHLH-PAS domain to interact with transcription factor in skeletal S.L. Dowhan D.H. Hosking B.M. Muscat G.E. Genes Dev. 2000; 14: 1209-1228Crossref PubMed Google Scholar). results additional evidence to the role of the bHLH-PAS domain as a motif used to the p160 proteins to transcription factors. The of the NRs transcriptional activity by the p160 proteins requires the recruitment of of the domain in its of the receptor transcriptional activity (33Bevan C.L. Hoare S. Claessens F. Heery D.M. Parker M.G. Mol. Cell. Biol. 1999; 19: 8383-8392Crossref PubMed Scopus (334) Google Scholar), but the was able to potentiate the TEF that SRC1 mechanisms to activate the is that the recruitment of protein via the C-terminal activation domain (19Chen D. Ma H. Hong H. Koh S.S. Huang S.M. Schurter B.T. Aswad D.W. Stallcup M.R. Science. 1999; 284: 2174-2177Crossref PubMed Scopus (1006) Google Scholar), or its histone activity M.M. J. N.J. S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Nature. 1997; PubMed Scopus Google Scholar), are in this are to C. P. B. P. H. and J. Chen for of I. and for and for J. for and M. E. and members of the Molecular for and reading of the
Belandia et al. (Sun,) studied this question.