Dj. Jung et al., Agonist-dependent repression mediated by mutant estrogen receptor alpha that lacks the activation function 2 core domain, J BIOL CHEM, 276(40), 2001, pp. 37280-37283
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, th
e ATPase constituent of the chromatin-remodeling SWI-SNF complex, and was a
bolished 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 an
d similar mutant receptors recently found associated with certain tumors ma
y actively perturb the normal E-2 signaling via SWI/SNF, N-CoR/SMRT, and HD
AC.