Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 8, Pages 5379-5387Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.275.8.5379
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Funding
- NCI NIH HHS [CA76636] Funding Source: Medline
- NIEHS NIH HHS [ES09106] Funding Source: Medline
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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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