Document Detail

Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90.
MedLine Citation:
PMID:  11911945     Owner:  NLM     Status:  MEDLINE    
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.
Mi Ock Lee; Eun Ok Kim; Ho Jeong Kwon; Young Mi Kim; Hyo Jin Kang; Heonjoong Kang; Jong Eun Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular endocrinology     Volume:  188     ISSN:  0303-7207     ISO Abbreviation:  Mol. Cell. Endocrinol.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-25     Completed Date:  2002-07-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7500844     Medline TA:  Mol Cell Endocrinol     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  47-54     Citation Subset:  IM    
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-dong, Kwangjin-gu, Seoul 143-747, South Korea.
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MeSH Terms
Binding Sites
Blotting, Northern
Blotting, Western
Breast Neoplasms / drug therapy,  genetics,  metabolism
Cells, Cultured
Cercopithecus aethiops
DNA / metabolism*
Down-Regulation / physiology*
Enzyme Inhibitors / pharmacology*
HSP90 Heat-Shock Proteins / metabolism*
Lactones / pharmacology*
Multienzyme Complexes / antagonists & inhibitors
Peptide Hydrolases / metabolism
Protease Inhibitors / pharmacology
Receptors, Estrogen / drug effects,  metabolism*
Regulatory Sequences, Nucleic Acid
Repressor Proteins / pharmacology*
Transcription, Genetic / genetics
Transcriptional Activation
Ubiquitins / metabolism
Reg. No./Substance:
0/Enzyme Inhibitors; 0/HSP90 Heat-Shock Proteins; 0/Lactones; 0/Macrolides; 0/Multienzyme Complexes; 0/Protease Inhibitors; 0/Receptors, Estrogen; 0/Repressor Proteins; 0/Ubiquitins; 12772-57-5/monorden; 9007-49-2/DNA; EC 3.4.-/Peptide Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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