Ligand-, cell-, and estrogen receptor subtype (α/β)-dependent activation at GC-rich (Sp1) promoter elements

被引:331
作者
Saville, B
Wormke, M
Wang, F
Nguyen, T
Enmark, E
Kuiper, G
Gustafsson, JÅ
Safe, S [1 ]
机构
[1] Texas A&M Univ, Dept Vet Physiol & Pharmacol, College Stn, TX 77843 USA
[2] Karolinska Inst, Novum, Ctr Biotechnol & Human Nutr, S-14186 Huddinge, Sweden
关键词
D O I
10.1074/jbc.275.8.5379
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
17 beta-Estradiol (E2) induces expression of several genes via estrogen receptor (ER)-Sp1 protein interactions with GC-rich promoter elements in which Sp1 but not ER binds DNA. This study reports the ligand- and cell context-dependent ERalpha/Sp1 and ERbeta/Sp1 action using an E2-responsive construct (pSp1) containing a GC-rich promoter. Both ERalpha and ERbeta proteins physically interact with Sp1 (coimmunoprecipitation) and preferentially bind to the C-terminal region of this protein in pull-down assays. E2- and antiestrogen-dependent transcriptional activation of ERalpha/Sp1 was observed in MCF-7, MDA-MB-231, and LnCaP cells, but not in HeLa cells. E2 did not affect or significantly decrease ERbeta/Sp1 action, and antiestrogens had minimal effects in the same 4 cell lines. Exchange of activation function-1 (AF-1) domains of ER subtypes gave chimeric ERalpha/beta (AF-2(alpha)/AF-2 beta) and ERbeta/alpha (AF-1 beta/AF-S alpha) proteins that resembled wild-type ER (alpha or beta) in terms of physical association with Sp1 protein. Transcriptional activation studies with chimeric ERBbeta/alpha and ERalpha/beta showed that only ERalpha/beta can activate transcription from an Sp1 element, not ERbeta/alpha. This indicates that the AF-1 domain from ERalpha is responsible for activation at an Sp1 element, independent of ER subtype context. In order to further characterize this observation, deletion constructs in the AF-1 domain of both ERalpha and ERalpha/beta were made, and transactivation studies indicated that the region between amino acids 79 and 117 of this domain is important for activation at an Sp1 element.
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收藏
页码:5379 / 5387
页数:9
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