G protein pathway suppressor 2 (GPS2) is a transcriptional corepressor important for estrogen receptor α-mediated transcriptional regulation

Xiwen Cheng, Hung Ying Kao

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

We have identified G protein suppressor 2 (GPS2) as a stable component of the SMRT corepressor complexes. GPS2 potently represses basal transcription, with the repression domain mapped to the N-terminal silencing mediator of retinoic acid and thyroid hormone receptor (SMRT)-interacting domain. Knockdown of GPS2 abrogates, whereas overexpression potentiates, SMRT-mediated repression activity. The SMRT complexes are involved in 4-hydroxyl-tamoxifen (4OHT)-mediated gene repression by estrogen receptor a (ERα). We show that 4OHT recruits SMRT and GPS2 to the promoter of pS2, an ERα target gene, in a dynamic manner. Unexpectedly, we also found that estradiol (E2) promotes promoter recruitment of the SMRT complexes. While knockdown of GPS2 compromised 4OHT-mediated repression, it enhanced E2-induced expression of a reporter gene and several endogenous ERα target genes, including pS2, cyclin D1 (CCND1), progesterone receptor (PR), and c-MYC. Finally, we show that depletion of GPS2 or SMRT by siRNA promotes cell proliferation in MCF-7 breast cancer cells. Thus, we concluded that GPS2 is an integral component of the SMRT complexes, important for ligand-dependent gene regulations by ERα and a suppressor for MCF-7 cell proliferation.

Original languageEnglish
Pages (from-to)36395-36404
Number of pages10
JournalJournal of Biological Chemistry
Volume284
Issue number52
DOIs
Publication statusPublished - 2009 Dec 25

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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