Steroid receptors are ligand-inducible transcription factors, and their association with steroid receptor coactivators (SRCs) upon binding to DNA is necessary for them to achieve full transcriptional potential. To understand the mechanism of SRC-1 action, its ability to interact and enhance the transcriptional activity of steroid receptors was analyzed. First, we show that SRC-1 is a modular coactivator that possesses intrinsic transcriptional activity when tethered to DNA and that it harbors two distinct activation domains, AD1 and AD2, needed for the maximum coactivation function of steroid receptors. We also demonstrate that SRC-1 interacts with both the amino-terminal A/B or AF1-containing domain and the carboxyl-terminal D/E or AF2-containing domain of the steroid receptors. These interactions are carried out by multiple regions of SRC-1, and they are relevant for transactivation. In addition to the inherent histone acetyltransferase activity of SRC-1, the presence of multiple receptor-coactivator interaction sites in SRC-1 and its ability to interact with components of the basic transcriptional machinery appears to be, at least in part, the mechanism by which the individual activation functions of the steroid receptors act cooperatively to achieve full transcriptional activity. Steroid receptors are ligand-inducible transcription factors, and their association with steroid receptor coactivators (SRCs) upon binding to DNA is necessary for them to achieve full transcriptional potential. To understand the mechanism of SRC-1 action, its ability to interact and enhance the transcriptional activity of steroid receptors was analyzed. First, we show that SRC-1 is a modular coactivator that possesses intrinsic transcriptional activity when tethered to DNA and that it harbors two distinct activation domains, AD1 and AD2, needed for the maximum coactivation function of steroid receptors. We also demonstrate that SRC-1 interacts with both the amino-terminal A/B or AF1-containing domain and the carboxyl-terminal D/E or AF2-containing domain of the steroid receptors. These interactions are carried out by multiple regions of SRC-1, and they are relevant for transactivation. In addition to the inherent histone acetyltransferase activity of SRC-1, the presence of multiple receptor-coactivator interaction sites in SRC-1 and its ability to interact with components of the basic transcriptional machinery appears to be, at least in part, the mechanism by which the individual activation functions of the steroid receptors act cooperatively to achieve full transcriptional activity. Steroid receptors belong to a superfamily of transcription factors that regulate hormone-responsive genes and thereby cellular growth and differentiation. In the absence of hormone, the receptor is maintained in an inactive or repressive state by association with heat shock proteins and/or corepressors. Activation of the aporeceptor by ligand binding involves structural and functional changes in the receptor molecule that promote release from the inactive or repressive state to bind specific DNA hormone response elements. In addition, the ligand-bound receptor promotes the recruitment of coactivators to the receptor-DNA complex and thus entitles the receptor to achieve its full transactivation capacity (for review, see Refs. 1Tsai M.J. O'Malley B.W. Annu. Rev. Biochem. 1994; 63: 451-486Crossref PubMed Scopus (2678) Google Scholar, 2Horwitz K.B. Jackson T.A. Bain D.L. Richer J.K. Takimoto G.S. Tung L. Mol. Endocrinol. 1996; 10: 1167-1177Crossref PubMed Scopus (834) Google Scholar, 3Perlmann T. Evans R.M. Cell. 1997; 90: 391-397Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 4Shibata H. Spencer T.E. Onate S.A., G., J. Tsai S.Y. Tsai M.-J. O'Malley B.W. Recent Prog. Horm. Res. 1997; 52: 1-25Google Scholar).Formation of the preinitiation complex at the promoter involves numerous general transcription factors that recruit RNA polymerase II binding to DNA and initiation of transcription (5Zawel L. Reinberg D. Annu. Rev. Biochem. 1995; 64: 533-561Crossref PubMed Scopus (389) Google Scholar). Steroid receptors activate target genes by stabilizing this preinitiation complex through direct interactions with components of the transcription machinery, including TFIIB, TATA-binding protein (TBP), TFIID, and TFIIF (6Ing N.H. Beekman J.M. Tsai S.Y. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1992; 267: 17617-17623Abstract Full Text PDF PubMed Google Scholar, 7Baniahmad Reinberg D. Tsai Tsai M.J. O'Malley B.W. 90: PubMed Scopus Google Scholar, L. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar, Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar, D. H. Evans R.M. 1995; PubMed Scopus Google Scholar, L. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Rev. 1996; PubMed Scopus Google Scholar, J. 1996; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, L. 1997; PubMed Scopus Google Scholar, J.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar). the mechanism by which receptors activate transcription is receptor and their activation steroid receptor TATA-binding activation steroid receptor TATA-binding that coactivators are also needed for receptor function L. H. J. Biol. Chem. 1992; 267: Full Text PDF PubMed Google Scholar, H. D. Cell. Full Text PDF PubMed Scopus Google Scholar). the the two transactivation functions and of a receptor that the of the individual activation functions of the steroid receptor is to the steroid receptor-DNA complex receptor coactivators and that they belong to a of proteins steroid receptor coactivators (SRCs) and SRC-1 Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. 1997; PubMed Scopus Google M.J. H. J. 1996; PubMed Scopus Google H. D.L. 1996; PubMed Scopus Google or J. J. 1997; PubMed Scopus Google and D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google H. 1997; PubMed Scopus Google J. J.M. 1997; PubMed Scopus Google J. J. 1997; PubMed Scopus Google or 1996; PubMed Scopus Google In addition, protein factors that interact with the receptor in a These and H. 1994; PubMed Scopus Google and J. 1995; PubMed Scopus Google 1995; PubMed Scopus Google Scholar, D. M.J. J.M. H. J. 1996; PubMed Scopus Google Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google J.M. L. D. H. J. 1995; PubMed Scopus Google 1997; Scopus Google and L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, D. T. H. Evans R.M. 1996; PubMed Scopus Google Scholar, J. H. 1996; PubMed Scopus Google Scholar). SRC-1, and are of receptor transcription activity in that SRC-1 interacts in with general transcription factors, and 1996; PubMed Scopus Google with L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, 1996; PubMed Scopus Google and J. J. 1997; PubMed Scopus Google that SRC-1 an in the interactions of receptor activation functions with the transcription machinery to transactivation. that of the SRC-1 and coactivator proteins and intrinsic histone acetyltransferase activity that receptors also recruit to for of the transcription machinery to DNA D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, T. 1996; PubMed Scopus Google Scholar, Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T.E. Onate Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar, Spencer T.E. Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar). mechanism by which steroid receptor coactivators transactivation function to understand the of coactivators in receptor action, we the of SRC-1 and the transcriptional activity of steroid receptors. We show that SRC-1 is a modular coactivator intrinsic activation functions for coactivation in We also show that SRC-1 is to interact with both the and the regions of steroid receptors. In addition, the and regions of the steroid appears to by SRC-1 and We that coactivators in a mechanism by which the of the steroid receptors a transcription complex target DNA of the mechanism by which receptors activate with the and of steroid receptor of receptor activity by coactivators is a complex and appears to at the for of receptor to DNA Rev. 1996; PubMed Scopus Google Scholar, D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, T. 1996; PubMed Scopus Google Scholar, Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T.E. Onate Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar, Spencer T.E. Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google interactions with components of the RNA polymerase II transcriptional machinery at the promoter of hormone-responsive genes (6Ing N.H. Beekman J.M. Tsai S.Y. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1992; 267: 17617-17623Abstract Full Text PDF PubMed Google Scholar, 7Baniahmad Reinberg D. Tsai Tsai M.J. O'Malley B.W. 90: PubMed Scopus Google Scholar, L. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar, Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar, D. H. Evans R.M. 1995; PubMed Scopus Google Scholar, L. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Rev. 1996; PubMed Scopus Google Scholar, J. 1996; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, L. 1997; PubMed Scopus Google Scholar, J.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar). with the of a we show that SRC-1 transcription when tethered to DNA by with a DNA binding of AD1 or the coactivation function of SRC-1 in the the of SRC-1 and its in coactivation and steroid receptor AD1 the basic which is the SRC-1 L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. 1997; PubMed Scopus Google Scholar, M.J. H. J. 1996; PubMed Scopus Google Scholar, H. D.L. 1996; PubMed Scopus Google Scholar, D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, H. 1997; PubMed Scopus Google Scholar, J. J.M. 1997; PubMed Scopus Google Scholar). at least in part, the intrinsic transcription activity in including M.J. H. J. 1996; PubMed Scopus Google Scholar, H. D.L. 1996; PubMed Scopus Google and H. 1997; PubMed Scopus Google Scholar). In of the of basic in and DNA binding for PubMed Scopus Google the intrinsic transcription activity of AD1 the of the direct with general transcription factors and/or the recruitment of factors of and of the preinitiation In of to to protein including SRC-1 of the activation domain and of the for the are for the mechanism by which SRC-1 steroid receptor least two for the hormone a at the amino-terminal A/B and the ligand-inducible at the D/E of the steroid receptors. domain an that is the steroid receptor superfamily J. 1992; PubMed Scopus Google Scholar). we that SRC-1 is of with both the A/B and D/E regions multiple receptor interaction receptor for SRC-1 was at the Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar). that this in SRC-1 is for interaction with the ligand binding D/E domain of the it interact with the A/B of steroid the carboxyl-terminal in SRC-1, is to for ligand-bound with the of SRC-1, also interacts with the D/E of the receptor in a in SRC-1 and receptor proteins to relevant for the interactions with and ligand binding Cell. Biol. 1997; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar). of this is that the SRC-1 from to also interacts with the in the A/B of of with the D/E to the with the A/B of In we that of SRC-1 are in the interactions with the A/B of in a of and bind to the and the to interact with in is in a interaction that this in SRC-1 cellular components for interaction with the A/B of in interaction of with the and AF2-containing regions of the receptor is to including and of interaction in are multiple interaction sites in the SRC-1 and in the receptor molecule that are for receptor-coactivator for SRC-1 distinct amino-terminal and carboxyl-terminal initiation and L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). To the that of SRC-1 of for SRC-1 for their ability to and We that a of SRC-1, the steroid receptor was the SRC-1 to that of SRC-1 relevant for activation of target steroid receptors are and the sites are at the amino-terminal A/B domain Mol. Endocrinol. 1995; PubMed Google Scholar, Mol. Endocrinol. 1997; PubMed Scopus Google the the that of steroid receptors SRC-1 of to and/or of the A/B of steroid receptors is in receptor-coactivator interactions and that the interactions and coactivation of steroid receptors by SRC-1 and are specific for transactivation of the steroid receptors M.J. H. J. 1996; PubMed Scopus Google Scholar, Cell. Biol. 1997; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, H. M.J. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). of coactivators to enhance the transcription activity of the A/B to the ability of to activate transcription by a mechanism from for coactivators H. M.J. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). we that are functional interactions of SRC-1 and with the and for steroid receptors These the that which to in the for are relevant for interactions and coactivation in We that SRC-1 interact with the receptor when both and are with the interactions with the individual SRC-1 when individual and of the steroid receptors in the mechanism by which the act in a the of their functional the of multiple coactivators and receptor-coactivator interaction sites to a mechanism by which steroid receptors achieve their and the of target Steroid receptors belong to a superfamily of transcription factors that regulate hormone-responsive genes and thereby cellular growth and differentiation. In the absence of hormone, the receptor is maintained in an inactive or repressive state by association with heat shock proteins and/or corepressors. Activation of the aporeceptor by ligand binding involves structural and functional changes in the receptor molecule that promote release from the inactive or repressive state to bind specific DNA hormone response elements. In addition, the ligand-bound receptor promotes the recruitment of coactivators to the receptor-DNA complex and thus entitles the receptor to achieve its full transactivation capacity (for review, see Refs. 1Tsai M.J. O'Malley B.W. Annu. Rev. Biochem. 1994; 63: 451-486Crossref PubMed Scopus (2678) Google Scholar, 2Horwitz K.B. Jackson T.A. Bain D.L. Richer J.K. Takimoto G.S. Tung L. Mol. Endocrinol. 1996; 10: 1167-1177Crossref PubMed Scopus (834) Google Scholar, 3Perlmann T. Evans R.M. Cell. 1997; 90: 391-397Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 4Shibata H. Spencer T.E. Onate S.A., G., J. Tsai S.Y. Tsai M.-J. O'Malley B.W. Recent Prog. Horm. Res. 1997; 52: 1-25Google Scholar). of the preinitiation complex at the promoter involves numerous general transcription factors that recruit RNA polymerase II binding to DNA and initiation of transcription (5Zawel L. Reinberg D. Annu. Rev. Biochem. 1995; 64: 533-561Crossref PubMed Scopus (389) Google Scholar). Steroid receptors activate target genes by stabilizing this preinitiation complex through direct interactions with components of the transcription machinery, including TFIIB, TATA-binding protein (TBP), TFIID, and TFIIF (6Ing N.H. Beekman J.M. Tsai S.Y. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1992; 267: 17617-17623Abstract Full Text PDF PubMed Google Scholar, 7Baniahmad Reinberg D. Tsai Tsai M.J. O'Malley B.W. 90: PubMed Scopus Google Scholar, L. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar, Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar, D. H. Evans R.M. 1995; PubMed Scopus Google Scholar, L. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Rev. 1996; PubMed Scopus Google Scholar, J. 1996; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, L. 1997; PubMed Scopus Google Scholar, J.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar). the mechanism by which receptors activate transcription is receptor and their activation steroid receptor TATA-binding activation steroid receptor TATA-binding that coactivators are also needed for receptor function L. H. J. Biol. Chem. 1992; 267: Full Text PDF PubMed Google Scholar, H. D. Cell. Full Text PDF PubMed Scopus Google Scholar). the the two transactivation functions and of a receptor that the of the individual activation functions of the steroid receptor is to the steroid receptor-DNA complex receptor coactivators and that they belong to a of proteins steroid receptor coactivators (SRCs) and SRC-1 Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. 1997; PubMed Scopus Google M.J. H. J. 1996; PubMed Scopus Google H. D.L. 1996; PubMed Scopus Google or J. J. 1997; PubMed Scopus Google and D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google H. 1997; PubMed Scopus Google J. J.M. 1997; PubMed Scopus Google J. J. 1997; PubMed Scopus Google or 1996; PubMed Scopus Google In addition, protein factors that interact with the receptor in a These and H. 1994; PubMed Scopus Google and J. 1995; PubMed Scopus Google 1995; PubMed Scopus Google Scholar, D. M.J. J.M. H. J. 1996; PubMed Scopus Google Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google J.M. L. D. H. J. 1995; PubMed Scopus Google 1997; Scopus Google and L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, D. T. H. Evans R.M. 1996; PubMed Scopus Google Scholar, J. H. 1996; PubMed Scopus Google Scholar). SRC-1, and are of receptor transcription activity in that SRC-1 interacts in with general transcription factors, and 1996; PubMed Scopus Google with L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, 1996; PubMed Scopus Google and J. J. 1997; PubMed Scopus Google that SRC-1 an in the interactions of receptor activation functions with the transcription machinery to transactivation. that of the SRC-1 and coactivator proteins and intrinsic histone acetyltransferase activity that receptors also recruit to for of the transcription machinery to DNA D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, T. 1996; PubMed Scopus Google Scholar, Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T.E. Onate Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar, Spencer T.E. Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar). mechanism by which steroid receptor coactivators transactivation function to To understand the of coactivators in receptor action, we the of SRC-1 and the transcriptional activity of steroid receptors. We show that SRC-1 is a modular coactivator intrinsic activation functions for coactivation in We also show that SRC-1 is to interact with both the and the regions of steroid receptors. In addition, the and regions of the steroid appears to by SRC-1 and We that coactivators in a mechanism by which the of the steroid receptors a transcription complex target DNA elements. of the mechanism by which receptors activate with the and of steroid receptor of receptor activity by coactivators is a complex and appears to at the for of receptor to DNA Rev. 1996; PubMed Scopus Google Scholar, D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, T. 1996; PubMed Scopus Google Scholar, Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T.E. Onate Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar, Spencer T.E. Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google interactions with components of the RNA polymerase II transcriptional machinery at the promoter of hormone-responsive genes (6Ing N.H. Beekman J.M. Tsai S.Y. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1992; 267: 17617-17623Abstract Full Text PDF PubMed Google Scholar, 7Baniahmad Reinberg D. Tsai Tsai M.J. O'Malley B.W. 90: PubMed Scopus Google Scholar, L. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar, Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar, D. H. Evans R.M. 1995; PubMed Scopus Google Scholar, L. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Rev. 1996; PubMed Scopus Google Scholar, J. 1996; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, L. 1997; PubMed Scopus Google Scholar, J.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar). with the of a we show that SRC-1 transcription when tethered to DNA by with a DNA binding of AD1 or the coactivation function of SRC-1 in the the of SRC-1 and its in coactivation and steroid receptor AD1 the basic which is the SRC-1 L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. 1997; PubMed Scopus Google Scholar, M.J. H. J. 1996; PubMed Scopus Google Scholar, H. D.L. 1996; PubMed Scopus Google Scholar, D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, H. 1997; PubMed Scopus Google Scholar, J. J.M. 1997; PubMed Scopus Google Scholar). at least in part, the intrinsic transcription activity in including M.J. H. J. 1996; PubMed Scopus Google Scholar, H. D.L. 1996; PubMed Scopus Google and H. 1997; PubMed Scopus Google Scholar). In of the of basic in and DNA binding for PubMed Scopus Google the intrinsic transcription activity of AD1 the of the direct with general transcription factors and/or the recruitment of factors of and of the preinitiation In of to to protein including SRC-1 of the activation domain and of the for the are for the mechanism by which SRC-1 steroid receptor least two for the hormone a at the amino-terminal A/B and the ligand-inducible at the D/E of the steroid receptors. domain an that is the steroid receptor superfamily J. 1992; PubMed Scopus Google Scholar). we that SRC-1 is of with both the A/B and D/E regions multiple receptor interaction receptor for SRC-1 was at the Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar). that this in SRC-1 is for interaction with the ligand binding D/E domain of the it interact with the A/B of steroid the carboxyl-terminal in SRC-1, is to for ligand-bound with the of SRC-1, also interacts with the D/E of the receptor in a in SRC-1 and receptor proteins to relevant for the interactions with and ligand binding Cell. Biol. 1997; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar). of this is that the SRC-1 from to also interacts with the in the A/B of of with the D/E to the with the A/B of In we that of SRC-1 are in the interactions with the A/B of in a of and bind to the and the to interact with in is in a interaction that this in SRC-1 cellular components for interaction with the A/B of in interaction of with the and AF2-containing regions of the receptor is to including and of interaction in are multiple interaction sites in the SRC-1 and in the receptor molecule that are for receptor-coactivator for SRC-1 distinct amino-terminal and carboxyl-terminal initiation and L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). To the that of SRC-1 of for SRC-1 for their ability to and We that a of SRC-1, the steroid receptor was the SRC-1 to that of SRC-1 relevant for activation of target steroid receptors are and the sites are at the amino-terminal A/B domain Mol. Endocrinol. 1995; PubMed Google Scholar, Mol. Endocrinol. 1997; PubMed Scopus Google the the that of steroid receptors SRC-1 of to and/or of the A/B of steroid receptors is in receptor-coactivator interactions and that the interactions and coactivation of steroid receptors by SRC-1 and are specific for transactivation of the steroid receptors M.J. H. J. 1996; PubMed Scopus Google Scholar, Cell. Biol. 1997; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, H. M.J. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). of coactivators to enhance the transcription activity of the A/B to the ability of to activate transcription by a mechanism from for coactivators H. M.J. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). we that are functional interactions of SRC-1 and with the and for steroid receptors These the that which to in the for are relevant for interactions and coactivation in We that SRC-1 interact with the receptor when both and are with the interactions with the individual SRC-1 when individual and of the steroid receptors in the mechanism by which the act in a the of their functional the of multiple coactivators and receptor-coactivator interaction sites to a mechanism by which steroid receptors achieve their and the of target of the mechanism by which receptors activate with the and of steroid receptor of receptor activity by coactivators is a complex and appears to at the for of receptor to DNA Rev. 1996; PubMed Scopus Google Scholar, D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, T. 1996; PubMed Scopus Google Scholar, Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, T.E. Onate Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google Scholar, Spencer T.E. Tsai S.Y. Tsai M.J. O'Malley B.W. 1997; PubMed Scopus Google interactions with components of the RNA polymerase II transcriptional machinery at the promoter of hormone-responsive genes (6Ing N.H. Beekman J.M. Tsai S.Y. Tsai M.-J. O'Malley B.W. J. Biol. Chem. 1992; 267: 17617-17623Abstract Full Text PDF PubMed Google Scholar, 7Baniahmad Reinberg D. Tsai Tsai M.J. O'Malley B.W. 90: PubMed Scopus Google Scholar, L. Cell. 1994; Full Text PDF PubMed Scopus Google Scholar, Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar, D. H. Evans R.M. 1995; PubMed Scopus Google Scholar, L. J. Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar, Rev. 1996; PubMed Scopus Google Scholar, J. 1996; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, L. 1997; PubMed Scopus Google Scholar, J.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar). with the of a we show that SRC-1 transcription when tethered to DNA by with a DNA binding of AD1 or the coactivation function of SRC-1 in the the of SRC-1 and its in coactivation and steroid receptor AD1 the basic which is the SRC-1 L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, J. J. 1997; PubMed Scopus Google Scholar, M.J. H. J. 1996; PubMed Scopus Google Scholar, H. D.L. 1996; PubMed Scopus Google Scholar, D. L. Evans R.M. Cell. 1997; 90: Full Text Full Text PDF PubMed Scopus Google Scholar, H. 1997; PubMed Scopus Google Scholar, J. J.M. 1997; PubMed Scopus Google Scholar). at least in part, the intrinsic transcription activity in including M.J. H. J. 1996; PubMed Scopus Google Scholar, H. D.L. 1996; PubMed Scopus Google and H. 1997; PubMed Scopus Google Scholar). In of the of basic in and DNA binding for PubMed Scopus Google the intrinsic transcription activity of AD1 the of the direct with general transcription factors and/or the recruitment of factors of and of the preinitiation In of to to protein including SRC-1 of the activation domain and of the for the are for the mechanism by which SRC-1 steroid receptor least two for the hormone a at the amino-terminal A/B and the ligand-inducible at the D/E of the steroid receptors. domain an that is the steroid receptor superfamily J. 1992; PubMed Scopus Google Scholar). we that SRC-1 is of with both the A/B and D/E regions multiple receptor interaction receptor for SRC-1 was at the Tsai S.Y. Tsai M.J. O'Malley B.W. 1995; PubMed Scopus Google Scholar). that this in SRC-1 is for interaction with the ligand binding D/E domain of the it interact with the A/B of steroid the carboxyl-terminal in SRC-1, is to for ligand-bound with the of SRC-1, also interacts with the D/E of the receptor in a in SRC-1 and receptor proteins to relevant for the interactions with and ligand binding Cell. Biol. 1997; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar). of this is that the SRC-1 from to also interacts with the in the A/B of of with the D/E to the with the A/B of In we that of SRC-1 are in the interactions with the A/B of in a of and bind to the and the to interact with in is in a interaction that this in SRC-1 cellular components for interaction with the A/B of in interaction of with the and AF2-containing regions of the receptor is to including and of interaction in are multiple interaction sites in the SRC-1 and in the receptor molecule that are for receptor-coactivator for SRC-1 distinct amino-terminal and carboxyl-terminal initiation and L. T. J. Cell. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). To the that of SRC-1 of for SRC-1 for their ability to and We that a of SRC-1, the steroid receptor was the SRC-1 to that of SRC-1 relevant for activation of target steroid receptors are and the sites are at the amino-terminal A/B domain Mol. Endocrinol. 1995; PubMed Google Scholar, Mol. Endocrinol. 1997; PubMed Scopus Google the the that of steroid receptors SRC-1 of to and/or of the A/B of steroid receptors is in receptor-coactivator interactions and transactivation. that the interactions and coactivation of steroid receptors by SRC-1 and are specific for transactivation of the steroid receptors M.J. H. J. 1996; PubMed Scopus Google Scholar, Cell. Biol. 1997; PubMed Scopus Google Scholar, 1997; PubMed Scopus Google Scholar, H. M.J. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). of coactivators to enhance the transcription activity of the A/B to the ability of to activate transcription by a mechanism from for coactivators H. M.J. Mol. Cell. Biol. 1997; PubMed Scopus Google Scholar). we that are functional interactions of SRC-1 and with the and for steroid receptors These the that which to in the for are relevant for interactions and coactivation in We that SRC-1 interact with the receptor when both and are with the interactions with the individual SRC-1 when individual and of the steroid receptors in the mechanism by which the act in a the of their functional the of multiple coactivators and receptor-coactivator interaction sites to a mechanism by which steroid receptors achieve their and the of target We for the the of for of and and for in of to
Oñate et al. (Fri,) studied this question.