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 ERα, while the amount of ubiquitinated ERα was increased. A proteasome inhibitor, LLnL, almost completely abrogated the radicicol-induced decrease in expression level, as well as in transcriptional activity of ERα. These results suggest that radicicol disrupts the ER-Hsp90 heterodimeric complex, thereby generating ERα that is susceptible to ubiquitin/proteasome-induced degradation.
Bibliographical noteFunding Information:
This work was supported by a grant from Korea Research Foundation (2000-015-DP0328).
All Science Journal Classification (ASJC) codes
- Molecular Biology