The ING1 gene was originally
cloned as a candidate tumor suppressor of human breast cancer, and recent
studies suggest that ING1 proteins are involved in chromatin remodeling
functions via physical association with both histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we investigated whether p33(ING1b), one of the major ING1 isoforms,
modulated the transcriptional activity of estrogen receptor (ER) alpha. In
Cos-7 cells transfected with increasing
concentrations of a mammalian expression vector encoding for p33(ING1b),
estrogen-induced ERalpha transcriptional activity was
found to increase in a dose-dependent manner. As p33(ING1b) expression levels
increased, transcription of an ER-responsive reporter gene by either
estrogen-inducible full-length ERalpha or activation
function (AF) 1 deletion mutant was enhanced, while the AF2 deletion mutant was
unaffected by the presence of p33(ING1b). These results showed that p33(ING1b) enhanced estrogen-induced ERalpha
activity through the AF2 domain. Our data also demonstrated that the antiestrogens inhibited the transcriptional activity of ERalpha as stimulated by p33(ING1b).
Furthermore, a weak physical association was observed between in vitro translated
p33(ING1b) and ERalpha. Our
data presented here demonstrate that p33(ING1b) acts
like a coactivator for ERalpha
and stimulates estrogen-induced ERalpha
transcriptional activity consistent with a function for p33(ING1b) in chromatin
remodeling.