Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90

Mi Ock Lee, Eun Ok Kim, Ho Jeong Kwon, Young Mi Kim, Hyo Jin Kang, Heonjoong Kang, Jongeun Lee

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)47-54
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume188
Issue number1-2
DOIs
Publication statusPublished - 2002 Feb 25

Fingerprint

HSP90 Heat-Shock Proteins
Estrogen Receptors
Stabilization
Estrogens
monorden
Thyroid Hormone Receptors
Degradation
Proteasome Inhibitors
Gene encoding
Proteasome Endopeptidase Complex
Transcription
Ubiquitin
Heat-Shock Proteins
Reporter Genes
Transcriptional Activation
Transcription Factors
Genes
Steroids
Hormones
Breast Neoplasms

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

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title = "Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90",
abstract = "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.",
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Radicicol represses the transcriptional function of the estrogen receptor by suppressing the stabilization of the receptor by heat shock protein 90. / Lee, Mi Ock; Kim, Eun Ok; Kwon, Ho Jeong; Kim, Young Mi; Kang, Hyo Jin; Kang, Heonjoong; Lee, Jongeun.

In: Molecular and Cellular Endocrinology, Vol. 188, No. 1-2, 25.02.2002, p. 47-54.

Research output: Contribution to journalArticle

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AU - Lee, Mi Ock

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AU - Kang, Heonjoong

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