PMID- 8816752 OWN - NLM STAT- MEDLINE DCOM- 19961113 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 93 IP - 19 DP - 1996 Sep 17 TI - Analysis of estrogen receptor transcriptional enhancement by a nuclear hormone receptor coactivator. PG - 10069-73 AB - The estrogen receptor (ER), a member of a large superfamily of nuclear hormone receptors, is a ligand-inducible transcription factor that regulates the expression of estrogen-responsive genes. The ER, in common with other members of this superfamily, contains two transcription activation functions (AFs)--one located in the amino-terminal region (AF-1) and the second located in the carboxyl-terminal region (AF-2). In most cell contexts, the synergistic activity of AF-1 and AF-2 is required for full estradiol (E2)-stimulated activity. We have previously shown that a ligand-dependent interaction between the two AF-containing regions of ER was promoted by E2 and the antiestrogen trans-hydroxytamoxifen (TOT). This interaction, however, was transcriptionally productive only in the presence of E2. To explore a possible role of steroid receptor coactivators in transcriptional synergism between AF-1 and AF-2, we expressed the amino terminal (AF-1-containing) and carboxyl-terminal (AF-2-containing) regions of ER as separate polypeptides in mammalian cells, along with the steroid receptor coactivator-1 protein (SRC-1). We demonstrate that SRC-1, which has been shown to significantly increase ER transcriptional activity, enhanced the interaction, mediated by either E2 or TOT, between the AF-1-containing and AF-2-containing regions of the ER. However, this enhanced interaction resulted in increased transcriptional effectiveness only with E2 and not with TOT, consistent with the effects of SRC-1 on the full-length receptor. Our results suggest that after ligand binding, SRC-1 may act, in part, as an adapter protein that promotes the integration of amino- and carboxyl-terminal receptor functions, allowing for full receptor activation. Potentially, SRC-1 may be capable of enhancing the transcriptional activity of related nuclear receptor superfamily members by facilitating the productive association of the two AF-containing regions in these receptors. FAU - McInerney, E M AU - McInerney EM AD - Department of Molecular and Integrative Physiology, University of Illinois, Urbana 61801, USA. FAU - Tsai, M J AU - Tsai MJ FAU - O'Malley, B W AU - O'Malley BW FAU - Katzenellenbogen, B S AU - Katzenellenbogen BS LA - eng GR - CA18119/CA/NCI NIH HHS/United States GR - CA60514/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (DNA-Binding Proteins) RN - 0 (Estrogen Antagonists) RN - 0 (IFNGR2 protein, human) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Interferon) RN - 0 (Recombinant Proteins) RN - 0 (Trans-Activators) RN - 094ZI81Y45 (Tamoxifen) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - CHO Cells MH - Cricetinae MH - DNA-Binding Proteins/*metabolism MH - Estradiol/*pharmacology MH - Estrogen Antagonists/pharmacology MH - Humans MH - Kinetics MH - Mammals MH - Polymerase Chain Reaction MH - Receptors, Estrogen/*metabolism MH - Receptors, Interferon MH - Recombinant Proteins/metabolism MH - Tamoxifen/pharmacology MH - Trans-Activators/*metabolism MH - Transcription, Genetic/*drug effects MH - Transfection PMC - PMC38337 EDAT- 1996/09/17 00:00 MHDA- 1996/09/17 00:01 PMCR- 1997/03/17 CRDT- 1996/09/17 00:00 PHST- 1996/09/17 00:00 [pubmed] PHST- 1996/09/17 00:01 [medline] PHST- 1996/09/17 00:00 [entrez] PHST- 1997/03/17 00:00 [pmc-release] AID - 10.1073/pnas.93.19.10069 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1996 Sep 17;93(19):10069-73. doi: 10.1073/pnas.93.19.10069.