TY - JOUR
T1 - Agonist-dependent Repression Mediated by Mutant Estrogen Receptor α that Lacks the Activation Function 2 Core Domain
AU - Jung, Dong Ju
AU - Lee, Soo Kyung
AU - Lee, Jae Woon
PY - 2001/10/5
Y1 - 2001/10/5
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M106860200
DO - 10.1074/jbc.M106860200
M3 - Article
C2 - 11487586
AN - SCOPUS:0035813142
SN - 0021-9258
VL - 276
SP - 37280
EP - 37283
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -