Agonist-dependent Repression Mediated by Mutant Estrogen Receptor α that Lacks the Activation Function 2 Core Domain

Dong Ju Jung, Soo Kyung Lee, Jae Woon Lee

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Nuclear receptor corepressor (N-CoR) and silencing mediator of retinoid and thyroid hormone receptors (SMRT) form heterogeneous complexes with various histone deacetylases (HDACs). In this report, we found that ERα-Δ AF2, a mutant estrogen receptor α (ERα) deleted for the C-terminal activation function 2 (AF2) core domain, directs estradiol (E 2)-dependent repression and impairs E2-induced transactivation by wild type ERα. This repression required coexpressed BRG1 in SW-13 cells that lack BRG1, the ATPase constituent of the chromatin-remodeling SWI·SNF complex, and was abolished by HDAC inhibitor trichostatin A. We further demonstrated that ERα-ΔAF2 constitutively associates with SMRT but binds DNA in an E2-dependent manner in vivo. These results suggest that ERα-ΔAF2 and similar mutant receptors recently found associated with certain tumors may actively perturb the normal E2 signaling via SWI/SNF, N-CoR/SMRT, and HDAC.

Original languageEnglish (US)
Pages (from-to)37280-37283
Number of pages4
JournalJournal of Biological Chemistry
Volume276
Issue number40
DOIs
StatePublished - Oct 5 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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