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Lee MO, Kim EO, Kwon HJ, Kim YM, Kang HJ, Kang H, Lee JE.
Radicicol represses the transcriptional function of the
estrogen receptor by suppressing the stabilization of the
receptor by heat shock protein 90.
Mol Cell Endocrinol. 2002 Feb 25;188(1-2):47-54
Department of Bioscience and Biotechnology, Sejong
University, 98 Kunja-dong, Kwangjin-gu, Seoul 143-747, South
Korea. molee@sejong.ac.kr
The estrogen receptor (ER) is a hormone-dependent transcription
factor that belongs to the steroid/thyroid hormone receptor
superfamily. Since the ER contributes to development and
progression in human breast cancer, a number of studies have
explored ways to inactivate this receptor. Previous studies have
suggested that the 90-kDa heat shock protein (Hsp90) interacts
with the ER, thus stabilizing the receptor in an inactive state.
Here, we report that radicicol, an Hsp90-specific inhibitor,
repressed estrogen-dependent transactivation of the ER as
measured by pS2 gene transcription and a reporter gene encoding
an estrogen-responsive element. Furthermore, we showed that
radicicol induced rapid degradation of ERalpha, while the amount
of ubiquitinated ERalpha was increased. A proteasome inhibitor,
LLnL, almost completely abrogated the radicicol-induced decrease
in expression level, as well as in transcriptional activity of
ERalpha. These results suggest that radicicol disrupts the
ER-Hsp90 heterodimeric complex, thereby generating ERalpha that
is susceptible to ubiquitin/proteasome-induced degradation.
PMID: 11911945
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