HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, H. S. Articles by White, J. H. Search for Related Content PubMed PubMed Citation Articles by Lee, H. S. Articles by White, J. H. Social Bookmarking                      What's this?

Volume 271, Number 42, Issue of October 18, 1996 pp. 25727-25730
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

---

COMMUNICATION:
Hormone-dependent Transactivation by Estrogen Receptor Chimeras That Do Not Interact with hsp90
EVIDENCE FOR TRANSCRIPTIONAL REPRESSORS

(Received for publication, December 26, 1995, and in revised form, July 2, 1996)

From the Department of Physiology, McGill University, Montreal, Quebec H3G 1Y6, Canada

The ligand-free estrogen receptor (ER), like other steroid receptors, interacts with the 90-kDa heat shock protein hsp90 in vitro. Analysis of the effect of potential ER-hsp90 interactions in vivo on receptor function is complicated by the fact that hsp90 binds to ER domains required for hormone binding and stable DNA binding. ER chimeras were therefore created by replacing the ER DNA binding domain with that of GAL4. In addition, the N-terminal AF-1 domain of the ER was replaced with the strong constitutive activation domain of VP16 to create VP16-GAL-ERs. These chimeras bind DNA in a ligand-independent manner, but, importantly, are ligand-dependent transactivators, unlike VP16-GAL, which displays strong constitutive activity under the same conditions. Hormone induces transactivation by VP16-GAL-ERs to levels similar to the constitutive activity of VP16-GAL. Glycerol gradient and coimmunoprecipitation experiments showed that, unlike the wild-type ER, VP16-GAL-ER chimeras do not interact with hsp90. Deletion analyses indicate that a region of the ER, primarily between amino acids 370 and 470, is responsible for repressed transcription. Our results suggest that interaction with hsp90 is not necessary for controlling hormone-dependent transcription by the ER and provide evidence for repressor factors that interact with the N-terminal portion of the receptor's ligand binding domain in the absence of hormone.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H.-J. Huang, J. D. Norris, and D. P. McDonnell Identification of a Negative Regulatory Surface within Estrogen Receptor {alpha} Provides Evidence in Support of a Role for Corepressors in Regulating Cellular Responses to Agonists and Antagonists Mol. Endocrinol., August 1, 2002; 16(8): 1778 - 1792. [Abstract] [Full Text] [PDF]

				L. Zheng, L. A. Annab, C. A. Afshari, W.-H. Lee, and T. G. Boyer BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor PNAS, August 1, 2001; (2001) 171174298. [Abstract] [Full Text] [PDF]

				R. Knoblauch and M. J. Garabedian Role for Hsp90-Associated Cochaperone p23 in Estrogen Receptor Signal Transduction Mol. Cell. Biol., May 1, 1999; 19(5): 3748 - 3759. [Abstract] [Full Text] [PDF]

				G. A. Stafford and R. H. Morse Mutations in the AF-2/Hormone-binding Domain of the Chimeric Activator GAL4·Estrogen Receptor·VP16 Inhibit Hormone-dependent Transcriptional Activation and Chromatin Remodeling in Yeast J. Biol. Chem., December 18, 1998; 273(51): 34240 - 34246. [Abstract] [Full Text] [PDF]

				W. Gong, S. Chávez, and M. Beato Point Mutation in the Ligand-Binding Domain of the Progesterone Receptor Generates a Transdominant Negative Phenotype Mol. Endocrinol., September 1, 1997; 11(10): 1476 - 1485. [Abstract] [Full Text]

				C. L. Smith, Z. Nawaz, and B. W. O’Malley Coactivator and Corepressor Regulation of the Agonist/Antagonist Activity of the Mixed Antiestrogen, 4-Hydroxytamoxifen Mol. Endocrinol., June 1, 1997; 11(6): 657 - 666. [Abstract] [Full Text]

				J. P. Aumais, H. S. Lee, R. Lin, and J. H. White Selective Interaction of hsp90 with an Estrogen Receptor Ligand-binding Domain Containing a Point Mutation J. Biol. Chem., May 2, 1997; 272(18): 12229 - 12235. [Abstract] [Full Text] [PDF]

				L. Zheng, L. A. Annab, C. A. Afshari, W.-H. Lee, and T. G. Boyer BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor PNAS, August 14, 2001; 98(17): 9587 - 9592. [Abstract] [Full Text] [PDF]