Ligand-dependent Interaction of Estrogen Receptor-α with Members of the Forkhead Transcription Factor Family

Eric R Schuur; Alexander V Loktev; Manju Sharma; Zijie Sun; Richard A Roth; Ronald J Weigel

doi:10.1074/jbc.M105555200

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Ligand-dependent Interaction of Estrogen Receptor-α with Members of the Forkhead Transcription Factor Family

Journal article

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Ligand-dependent Interaction of Estrogen Receptor-α with Members of the Forkhead Transcription Factor Family

Eric R Schuur, Alexander V Loktev, Manju Sharma, Zijie Sun, Richard A Roth and Ronald J Weigel

The Journal of biological chemistry, Vol.276(36), pp.33554-33560

09/07/2001

DOI: 10.1074/jbc.M105555200

PMID: 11435445

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Abstract

Estrogen acting through the estrogen receptor (ER) is able to regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors. Ligand-activated ER binds DNA and transactivates the promoters of estrogen target genes. In addition, ligand-activated ER can interact with other factors to alter the physiology and growth of cells. Using a yeast two-hybrid screen, we have identified an interaction between ERα and the proapoptotic forkhead transcription factor FKHR. The ERα-FKHR interaction depends on β-estradiol and is reduced significantly in the absence of hormone or the presence of Tamoxifen. A glutathione S-transferase pull-down assay was used to confirm the interaction and localized two interaction sites, one in the forkhead domain and a second in the carboxyl terminus. The FKHR interaction was specific to ERα and was not detected with other ligand-activated steroid receptors. The related family members, FKHRL1 and AFX, also bound to ERα in the presence of β-estradiol. FKHR augmented ERα transactivation through an estrogen response element. Conversely, ERα repressed FKHR-mediated transactivation through an insulin response sequence, and cell cycle arrest induced by FKHRL1 in MCF7 cells was abrogated by estradiol. These results suggest a novel mechanism of estrogen action that involves regulation of the proapoptotic forkhead transcription factors.

Details

Title: Subtitle: Ligand-dependent Interaction of Estrogen Receptor-α with Members of the Forkhead Transcription Factor Family
Creators: Eric R Schuur
Alexander V Loktev
Manju Sharma
Zijie Sun
Richard A Roth
Ronald J Weigel
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.276(36), pp.33554-33560
DOI: 10.1074/jbc.M105555200
PMID: 11435445
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Language: English
Date published: 09/07/2001
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984024558102771

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