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

Dong Ju Jung, Soo-Kyung Lee, Jae Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

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
Externally publishedYes

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Estrogen Receptors
Chemical activation
Histone Deacetylases
Co-Repressor Proteins
trichostatin A
Thyroid Hormone Receptors
Chromatin Assembly and Disassembly
Retinoids
Transcriptional Activation
Chromatin
Adenosine Triphosphatases
Tumors
Estradiol
DNA
Neoplasms

ASJC Scopus subject areas

  • Biochemistry

Cite this

Agonist-dependent Repression Mediated by Mutant Estrogen Receptor α that Lacks the Activation Function 2 Core Domain. / Jung, Dong Ju; Lee, Soo-Kyung; Lee, Jae.

In: Journal of Biological Chemistry, Vol. 276, No. 40, 05.10.2001, p. 37280-37283.

Research output: Contribution to journalArticle

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