The agonist-induced androgen receptor NH2- and COOH-terminal (N/C) interaction is mediated by the FXXLF and WXXLF NH2-terminal motifs. Here we demonstrate that agonist-dependent transactivation of prostate-specific antigen (PSA) and probasin enhancer/promoter regions requires the N/C interaction, whereas the sex-limited protein gene and mouse mammary tumor virus long terminal repeat do not. Transactivation of PSA and probasin response regions also depends on activation function 1 (AF1) in the NH2-terminal region but can be increased by binding an overexpressed p160 coactivator to activation function 2 (AF2) in the ligand binding domain. The dependence of the PSA and probasin enhancer/promoters on the N/C interaction for transactivation allowed us to demonstrate that in the presence of androgen, the WXXLF motif with the sequence433WHTLF437 contributes as an inhibitor to AR transactivation. We further show that like the FXXLF and LXXLL motifs, the WXXLF motif interacts in the presence of androgen with AF2 in the ligand binding domain. Sequence comparisons among species indicate greater conservation of the FXXLF motif compared with the WXXLF motif, paralleling the functional significance of these binding motifs. The data provide evidence for promoter-specific differences in the requirement for the androgen receptor N/C interaction and in the contributions of AF1 and AF2 in androgen-induced gene regulation. The agonist-induced androgen receptor NH2- and COOH-terminal (N/C) interaction is mediated by the FXXLF and WXXLF NH2-terminal motifs. Here we demonstrate that agonist-dependent transactivation of prostate-specific antigen (PSA) and probasin enhancer/promoter regions requires the N/C interaction, whereas the sex-limited protein gene and mouse mammary tumor virus long terminal repeat do not. Transactivation of PSA and probasin response regions also depends on activation function 1 (AF1) in the NH2-terminal region but can be increased by binding an overexpressed p160 coactivator to activation function 2 (AF2) in the ligand binding domain. The dependence of the PSA and probasin enhancer/promoters on the N/C interaction for transactivation allowed us to demonstrate that in the presence of androgen, the WXXLF motif with the sequence433WHTLF437 contributes as an inhibitor to AR transactivation. We further show that like the FXXLF and LXXLL motifs, the WXXLF motif interacts in the presence of androgen with AF2 in the ligand binding domain. Sequence comparisons among species indicate greater conservation of the FXXLF motif compared with the WXXLF motif, paralleling the functional significance of these binding motifs. The data provide evidence for promoter-specific differences in the requirement for the androgen receptor N/C interaction and in the contributions of AF1 and AF2 in androgen-induced gene regulation. activation function 1 androgen receptor NH2-terminal and COOH-terminal activation function 2 transcriptional intermediary factor 2 glutathione S-transferase glucocorticoid receptor luciferase prostate-specific antigen mouse mammary tumor virus dihydrotestosterone Steroid receptors are ligand-activated transcription factors that regulate gene activation through a series of events triggered by high affinity hormone binding and mediated by receptor binding to response element DNA and coactivators. At least two domains have been identified that mediate nuclear receptor interactions with coregulators. These are activation function 1 (AF1)1in the NH2-terminal region and activation function 2 (AF2) in the ligand binding domain. The AF2 binding surface in the ligand binding domain is comprised of helices 3, 4, and 12 and forms after hormone binding. For many nuclear receptors, transactivation depends on AF2 recruitment of p160 coactivator complexes that have histone acetyl transferase activity to modify chromatin structure (1Spencer T.E. Jenster G. Burcin M.M. Allis C.D. Zhou J. Mizzen C.A. McKenna N.J. Onate S.A. Tsai S.Y. Tsai M.J. O'Malley B.W. Nature. 1997; 389: 194-198Crossref PubMed Scopus (1070) Google Scholar). The p160 coactivators are a group of proteins that include steroid receptor coactivator 1 (SRC1), transcriptional intermediary protein 2 (TIF2, GRIP1 or SRC2), and the steroid receptor coactivator 3 subfamily (SRC3). Interaction with AF2 is mediated by the p160 coactivator LXXLL motif that forms an amphipathic α-helix and binds the AF2 hydrophobic binding surface in the nuclear receptor ligand binding domain (2Heery D.M. Kalkhoven E. Hoare S. Parker M.G. Nature. 1997; 387: 733-736Crossref PubMed Scopus (1778) Google Scholar, 3Darimont B.D. Wagner R.L. Apriletti J.W. Stallcup M.R. Kushner P.J. Baxter J.D. Fletterick R.J. Yamamoto K.R. Genes Dev. 1998; 12: 3343-3356Crossref PubMed Scopus (832) Google Scholar, 4Nolte R.T. Wisely G.B. Westin S. Cobb J.E. Lambert M.H. Kurokawa R. Rosenfeld M.G. Willson T.M. Glass C.K. Milburn M.V. Nature. 1998; 395: 137-143Crossref PubMed Scopus (1700) Google Scholar, 5Shiau A.K. Barstad D. Loria P.M. Cheng L. Kushner P.J. Agard D.A. Greene G.L. Cell. 1998; 95: 927-937Abstract Full Text Full Text PDF PubMed Scopus (2269) Google Scholar). For the androgen receptor (AR), the functional importance of AF2 recruitment of p160 coactivators is unclear, with data implicating the AR NH2-terminal AF1 region in AR-mediated gene activation. The AF2 binding site in the AR ligand binding domain was shown to mediate the agonist-induced NH2- and COOH-terminal (N/C) interaction (6Wong C.I. Zhou Z.X. Sar M. Wilson E.M. J. Biol. Chem. 1993; 268: 19004-19012Abstract Full Text PDF PubMed Google Scholar, 7Zhou Z.X. Lane M.V. Kemppainen J.A. French F.S. Wilson E.M. Mol. Endocrinol. 1995; 9: 208-218Crossref PubMed Google Scholar, 8Langley E. Zhou Z.X. Wilson E.M. J. Biol. Chem. 1995; 270: 29983-29990Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar, 9Langley E. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 1998; 273: 92-101Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar, 10He B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar). Agonist-induced N/C interdomain interactions are also reported for the estrogen (11Kraus W.L. McInerney E.M. Katzenellenbogen B.S. Proc. Natl. Acad. Sci. U. S. A. 1995; 92: 12314-12318Crossref PubMed Scopus (184) Google Scholar) and progesterone receptors (12Tetel M.J. Giangrande P.H. Leonhardt S.A. McDonnell D.P. Edwards D.P. Mol. Endocrinol. 1999; 13: 910-924Crossref PubMed Google Scholar), but not for the glucocorticoid receptor (GR) (7Zhou Z.X. Lane M.V. Kemppainen J.A. French F.S. Wilson E.M. Mol. Endocrinol. 1995; 9: 208-218Crossref PubMed Google Scholar, 13He B. Bowen N.T. Minges J.T. Wilson E.M. J. Biol. Chem. 2001; 276: 42293-42301Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar). Two AR NH2-terminal LXXLL-like motifs that interact with the AR ligand binding domain are the FXXLF and WXXLF motifs (23FQNLF27 and433WHTLF437) (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). Mutagenesis studies and mammalian two-hybrid and GST affinity matrix assays demonstrated that the FXXLF motif interacts in the presence of androgen with AF2 (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). However the site of interaction of the WXXLF motif was not determined, nor was it clear whether interaction of the WXXLF motif depends on androgen binding. In addition, previous studies made use of the MMTV luciferase reporter vector, which may direct transcription through mechanisms that differ from other androgen responsive enhancer/promoters. Here we show the functional importance of the AR N/C interaction using androgen responsive enhancer/promoter regions derived from the antigen (PSA) and probasin of these responsive regions allowed us to in addition, that the WXXLF motif recruitment of by the AF2 region but the FXXLF a NH2-terminal (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar), we show that the WXXLF motif interacts in the presence of androgen with the AF2 region of the ligand binding domain. The data provide evidence that the AR N/C interaction is for AR-mediated of two The high conservation of the FXXLF and WXXLF motifs among species further the functional importance of the AR N/C proteins as B. Minges J.T. Wilson E.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and DNA binding domain and the with AR or with and for in (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). was by the in the and the with the is to was in the by using the region of the is to and which in to B. Bowen N.T. Minges J.T. Wilson E.M. J. Biol. Chem. 2001; 276: 42293-42301Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, B. Minges J.T. Wilson E.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). was by using the in and using a The was with the and by and B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar) and the ligand binding domain with the was using a The AR NH2-terminal region of was using a the the and a of the The and with the DNA by was using regions of DNA that using to the of The and B. Bowen N.T. Minges J.T. Wilson E.M. J. Biol. Chem. 2001; 276: 42293-42301Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar). which a androgen responsive enhancer/promoter region was by The that the sex-limited protein androgen responsive was by M. of which the androgen responsive probasin enhancer/promoter was by J. mammary tumor virus was by M. the for The mammalian for was by of was by in and 2 with and AR and luciferase reporter using the DNA B. Bowen N.T. Minges J.T. Wilson E.M. J. Biol. Chem. 2001; 276: 42293-42301Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar). of and with of or 2 of the of and with of or in for with or hormone as in of 2 and was using an in with and 2 and in and using of or of and of and the in of and and by the using of 1 of 1 of and of and The DNA was for in and 2 of was for in the and presence of the and for luciferase activity as in of GST proteins in with and and with as (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). In proteins in the presence of of using the in the presence and of 1 dihydrotestosterone in and of the binding We whether androgen response regions derived from enhancer/promoter regions have a requirement for the androgen-induced N/C interaction in AR-mediated gene regulation. reporter that enhancer/promoter regions from the PSA J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J. Mol. Endocrinol. 1997; PubMed Scopus Google Scholar), probasin S.A. Cheng H. R. A. B.S. S. R.J. Mol. Endocrinol. 1993; PubMed Scopus Google Scholar), sex-limited protein J. M. D.M. Mol. Cell. Biol. PubMed Scopus Google Scholar, A. E. D.M. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar), and MMTV G. M. PubMed Scopus Google Scholar, B. J. PubMed Scopus Google Scholar, M.G. G.L. Cell. Full Text PDF PubMed Scopus Google Scholar). The of the WXXLF and FXXLF motifs and of on luciferase activity using AR or AR in which FXXLF was to WXXLF was to or in the AR transactivation of the PSA and probasin enhancer/promoter regions 1 and the and MMTV 1 was increased by of the FXXLF motif to transactivation of the PSA and probasin luciferase in the of 1 in activity was by of In of the FXXLF motif on transactivation of the and enhancer/promoters in the of 1 of the WXXLF motif increased the response of the PSA and probasin which was increased further by 1 In of WXXLF on the response of and 1 binding motifs transactivation of the PSA and probasin which was by of 1 with on the and MMTV The indicate that in to the and MMTV androgen of the PSA and probasin enhancer/promoter regions depends on the AR N/C interaction mediated by the FXXLF and WXXLF motifs in the presence of The in transactivation by WXXLF an of motif in AR whereas a in transactivation by the and a requirement for the N/C The are in with the FXXLF motif the N/C interaction, whereas of the WXXLF motif not the N/C interaction (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). The on transactivation of the N/C interaction was by The previous evidence from androgen E. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 1998; 273: 92-101Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar) the N/C interaction is for AR-mediated transactivation of in We further the of the WXXLF motif in AR-mediated transactivation of the PSA enhancer/promoter by the WXXLF and FXXLF binding motifs in an AR in which the NH2-terminal AF1 of AF1 in of activity in the or presence of an for AF1 in AR-mediated transactivation. the FXXLF and FXXLF WXXLF motifs increased AR-mediated transactivation of the reporter in the and presence of the WXXLF motif was in the AF1 was a in transactivation by using the reporter not We that in the of FXXLF and WXXLF motifs have a on AR transactivation in the of was a by motifs, of through AF2 in the ligand binding domain. The greater of luciferase activity with the FXXLF compared with the WXXLF that FXXLF AR-mediated gene activation by The in luciferase activity of the further evidence that the WXXLF motif contributes to by of the WXXLF motif not transactivation by of PSA and probasin luciferase activity with the WXXLF 1 to on AF1 the in activity was the WXXLF was in the AF1 further the requirement for the N/C interaction in transactivation of the PSA enhancer/promoter the MMTV we made use of a in which an N/C interaction was B. Bowen N.T. Minges J.T. Wilson E.M. J. Biol. Chem. 2001; 276: 42293-42301Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar). the 3 LXXLL motif region of that interacts in the presence of with the ligand binding domain AF2 region and in a of compared with In the presence of 1 or the PSA and probasin not and the MMTV 3 and luciferase not with the response from greater transactivation of the reporter or in which the 3 LXXLL motifs to 3 in gene activation by using the and not In response of the reporter was for and the 3 The that transactivation of the androgen responsive enhancer/promoters from PSA and probasin on an agonist-induced N/C interaction for transactivation compared with the MMTV The increased response of to that it of PSA and probasin response that are to the of an N/C We whether the in AR transactivation of and by binding to the AF2 region of the ligand binding domain. In to a in which the 3 LXXLL motifs to was to AR or the AR N/C interaction using the reporter Transactivation in the presence of was the using the probasin and not The data that by of of the requires interaction of the LXXLL motifs with the AR AF2 region and that to a as a inhibitor of The of by in addition, that an interaction other regions of and the AR NH2-terminal region B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, G. B. Mol. Cell. Biol. 1999; PubMed Scopus Google Scholar, Hoare S. D.M. Parker M.G. Mol. Cell. Biol. 1999; PubMed Scopus Google Scholar) not to mediate increased transactivation. for AF2 in AR transactivation of the reporter by was using two AR AF2 in 3 of the ligand binding domain is for coactivator LXXLL motif but not for the binding of the AR NH2-terminal FXXLF motif (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). in 12 of the ligand binding domain is for LXXLL motif binding and the N/C interactions (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). not AR-mediated transactivation of the reporter in the of but by AR activity and by AR transactivation was not by AR of these AF2 and the N/C interaction was by in the FXXLF and WXXLF motifs. The indicate that of AR requires binding to we a GST affinity matrix to the of androgen on the interaction of the FXXLF and WXXLF motifs with the ligand binding domain. We demonstrated an interaction of the FXXLF motif with but with the WXXLF motif (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). binding in the of androgen of a the WXXLF motif the that of the binding was (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). We a with a the WXXLF of AR ligand binding domain in the presence in the of In addition, of to in the WXXLF motif in the interaction and The indicate that the WXXLF motif binds the AR ligand binding domain in an The amphipathic structure of the WXXLF and the hormone dependence of interaction with the ligand binding domain that the WXXLF motif interacts with the AF2 binding We a series of AF2 that shown to or LXXLL motif binding R.T. Wisely G.B. Westin S. Cobb J.E. Lambert M.H. Kurokawa R. Rosenfeld M.G. Willson T.M. Glass C.K. Milburn M.V. Nature. 1998; 395: 137-143Crossref PubMed Scopus (1700) Google Scholar, 5Shiau A.K. Barstad D. Loria P.M. Cheng L. Kushner P.J. Agard D.A. Greene G.L. Cell. 1998; 95: 927-937Abstract Full Text Full Text PDF PubMed Scopus (2269) Google Scholar, 10He B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar) and the binding of the AR FXXLF motif in the N/C interaction B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). AR AF2 and the ligand binding domain or binding of of the in the presence of androgen was and greater that of the and in the presence of androgen, on of the The ligand binding domain mediated a in binding of the WXXLF in the presence of androgen to the hormone but androgen in binding was with the and ligand binding domain. and are of the AF2 binding The is in the AF2 hydrophobic to the hydrophobic binding surface as also shown in GST affinity matrix assays for FXXLF motif binding B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar), is the to WXXLF motif binding. The data provide evidence that the WXXLF motif binds the AF2 region of the ligand binding domain in an further the binding of the WXXLF motif to we a two-hybrid interaction in B. Minges J.T. Wilson E.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). binding domain protein was to the DNA binding domain and of the WXXLF was with an AR in which in NH2-terminal binding motifs and in the motif to to the and interdomain N/C in the presence of androgen, with an in luciferase activity greater that with The of interaction of the WXXLF was that with a protein the region of the FXXLF motif that AF2 in the AR ligand binding domain is the binding site for the WXXLF motif, the two AF2 and by of the two the WXXLF or FXXLF motifs was interaction with in the presence of In the FXXLF motif as by the in luciferase Interaction with was for the FXXLF and WXXLF In studies not the WXXLF motif as with AR as it with it not interact with an AF2 in which the NH2-terminal binding motifs not of the AF2 a in the androgen binding affinity B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar). The indicate binding of the WXXLF motif to the AF2 region of the ligand binding domain that is that with the FXXLF The greater dependence of the WXXLF on differences in the AF2 binding surface for the FXXLF and WXXLF the binding site for WXXLF the binding site for the LXXLL motif B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar). Here we that enhancer/promoter regions derived from the PSA and probasin the androgen-induced N/C interaction for AR-mediated transactivation. the enhancer/promoter region of MMTV that was with to the presence of the N/C interaction for transactivation by The dependence of the enhancer/promoter regions of the PSA and probasin on the N/C interaction allowed us to in addition, that in the presence of androgen, the WXXLF motif a but the FXXLF motif in the N/C interaction and in the recruitment of to the FXXLF motif, WXXLF was not for the androgen-induced N/C interaction, with that WXXLF not the ligand (14He B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). The WXXLF motif is in affinity for AF2 and in to binding. The amphipathic α-helix and androgen dependence of the WXXLF motif interaction with the ligand binding domain interaction with GST affinity matrix and two-hybrid interaction assays The of the WXXLF motif in AR transactivation was in WXXLF increased AR transactivation of the PSA and probasin enhancer/promoters. in a the NH2-terminal AF1 the WXXLF not the of the FXXLF motif on recruitment by comparisons the functional importance of the FXXLF and WXXLF binding motifs. is among Kemppainen J.A. Wilson E.M. J. Mol. 1998; PubMed Scopus Google Scholar, J.A. Sar M. French F.S. Wilson E.M. Mol. Endocrinol. PubMed Scopus Google Scholar, J. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, N.J. Zhou Z.X. Wilson E.M. French F.S. Mol. Endocrinol. PubMed Scopus Google Scholar, S. PubMed Scopus Google Scholar) paralleling in the N/C interaction and in AF2 to p160 coactivators. In and in 1 of the motif, and in these and AR and These the amphipathic structure that a binding motif for is not whether an N/C interaction in the AR of these In with in the N/C interaction, is in and but in is is but is other that an amphipathic α-helix is not for the WXXLF motif region in previous studies of ligand two-hybrid interactions and GST affinity matrix binding an androgen-induced N/C interaction by E. Zhou Z.X. Wilson E.M. J. Biol. Chem. 1995; 270: 29983-29990Abstract Full Text Full Text PDF PubMed Scopus (235) Google Scholar, 9Langley E. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 1998; 273: 92-101Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar, 10He B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar). we that that the androgen the N/C interaction androgen binding affinity E. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 1998; 273: 92-101Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar, 10He B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar). we evidence for the functional importance of the N/C interaction in that the reporter was by but not the N/C interaction for activation B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar, B. Kemppainen J.A. Wilson E.M. J. Biol. Chem. 2000; 275: 22986-22994Abstract Full Text Full Text PDF PubMed Scopus (365) Google Scholar). The for the N/C interaction in AR transactivation of the androgen responsive PSA and probasin enhancer/promoters reported a greater dependence on the N/C interaction was for transactivation of the MMTV and The in transactivation mediated by a with an N/C interaction demonstrated further the of an N/C interaction on transactivation of the PSA and probasin enhancer/promoter AR transactivation to be mediated by the NH2-terminal AF1 region of AF1 in of AR transactivation of the androgen responsive enhancer/promoters in The in transactivation that from WXXLF in the or presence of requires AF1 and is also by in The that the increased transactivation by WXXLF a AF1 and AF2 by AF2 to activation by coactivators as In with the WXXLF motif binds AF2 and AF2 mediated transactivation by the binding of to a the FXXLF The data that the N/C interaction that is mediated by binding of the FXXLF and WXXLF motifs to AF2 p160 coactivator interaction of AF2 by the androgen-induced N/C interaction AF1 the activation domain in AR coactivator the of the N/C interaction to coactivator binding. of evidence the of AF1 in AR transactivation. The AF2 that binding to AF2 B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar) not AR-mediated transactivation in response to The agonist-induced N/C interaction mediated by the FXXLF and WXXLF motifs in of p160 coactivator binding AF2 binds the FXXLF compared with the LXXLL of the p160 coactivators B. Minges J.T. Wilson E.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). p160 coactivator was in compared with B. R.T. French F.S. Wilson E.M. 2001; Google Scholar). is clear that AR transactivation can be increased by which LXXLL motifs to for interaction with in of high as in B. R.T. French F.S. Wilson E.M. 2001; Google Scholar), AR transactivation may be mediated by AF1 and We B. Kemppainen J.A. Voegel J.J. Gronemeyer H. Wilson E.M. J. Biol. Chem. 1999; 274: 37219-37225Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar) and G. B. Mol. Cell. Biol. 1999; PubMed Scopus Google Scholar, Hoare S. D.M. Parker M.G. Mol. Cell. Biol. 1999; PubMed Scopus Google Scholar) have reported that and other p160 coactivators interact with the AR NH2-terminal domain. In the using the PSA and probasin in AF2 of AR transactivation. interaction of overexpressed with the AR NH2-terminal domain was to binding to In of which in the LXXLL motifs, was in the presence and of the N/C interaction using the and that interaction with AF2 is for AR The with previous that GRIP1 and interactions with the AR NH2-terminal domain are for of AR transactivation G. B. Mol. Cell. Biol. 1999; PubMed Scopus Google Scholar, Hoare S. D.M. Parker M.G. Mol. Cell. Biol. 1999; PubMed Scopus Google Scholar). The differences that p160 coactivators may use mechanisms to AR-mediated gene activation. is not clear of the enhancer/promoter regions the N/C interaction in AR transactivation. as MMTV receptor and is by the and the progesterone receptor D. H. J. PubMed Scopus Google Scholar, M.M. Mol. Endocrinol. PubMed Scopus Google Scholar). enhancer/promoters show of for AR transactivation. In the and probasin luciferase by AR and whereas was transactivation of is that the MMTV G. M. PubMed Scopus Google Scholar, B. J. PubMed Scopus Google Scholar, M.G. G.L. Cell. Full Text PDF PubMed Scopus Google Scholar), whereas the probasin R. M. M. R. R.J. Mol. Endocrinol. PubMed Scopus Google Scholar, S. Cheng H. L. R. R.J. J. Biol. Chem. Full Text PDF PubMed Google Scholar) and A. E. D.M. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar) enhancer/promoters are reported to be by was the probasin and enhancer/promoters that increased transactivation by the with an N/C At are that these enhancer/promoter androgen response in of to the N/C We that the differences in a receptor N/C interaction to the or of the response of as PSA and probasin that have not been to to have response compared with AR mediated by the N/C interaction in the AR of DNA in a that response and provide response through and mechanisms that to be We S. French for the and the of Cobb and by J. D. M. R. J. D. H. and R. M.
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