Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 276 (40), 37280-3

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

Affiliations

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

D J Jung et al. J Biol Chem.

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 ER alpha-Delta AF2, a mutant estrogen receptor alpha (ER alpha) deleted for the C-terminal activation function 2 (AF2) core domain, directs estradiol (E(2))-dependent repression and impairs E(2)-induced transactivation by wild type ER alpha. 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 ER alpha-Delta AF2 constitutively associates with SMRT but binds DNA in an E(2)-dependent manner in vivo. These results suggest that ER alpha-Delta AF2 and similar mutant receptors recently found associated with certain tumors may actively perturb the normal E(2) signaling via SWI/SNF, N-CoR/SMRT, and HDAC.

Similar articles

See all similar articles

Cited by 7 articles

See all "Cited by" articles

Publication types

MeSH terms

Feedback