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Molecular and Cellular Biology, October 2003, p. 7189-7197, Vol. 23, No. 20
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.20.7189-7197.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

The Cochaperone Bag-1L Enhances Androgen Receptor Action via Interaction with the NH2-Terminal Region of the Receptor

Liubov Shatkina,1 Sigrun Mink,2 Hermann Rogatsch,3 Helmut Klocker,4 Gernot Langer,5 Andrea Nestl,1 and Andrew C. B. Cato1*

Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, D-76021 Karlsruhe,1 62M Cancer Drugs AG, Forschungszentrum Karlsruhe, D-76344 Eggenstein-Leopoldshafen,2 Research Laboratories of Schering AG, D-13342 Berlin, Germany,5 Departments of Pathology,3 Urology, University of Innsbruck, A-6020 Innsbruck, Austria4

Received 8 May 2003/ Returned for modification 4 June 2003/ Accepted 16 July 2003

Members of the Bag-1 family of cochaperones regulate diverse cellular processes including the action of steroid hormone receptors. The largest member of this family, Bag-1L, enhances the transactivation function of the androgen receptor. This occurs primarily through interaction with the NH2 and COOH termini of the receptor. At the NH2 terminus of the receptor, Bag-1L interacts with a region termed {tau}5. Bag-1M, a naturally occurring variant of Bag-1L that binds to {tau}5 but is defective in the COOH-terminal interaction, is less efficient in enhancing the transactivation function of the receptor. Surface plasmon resonance and transfection studies showed that the molecular chaperone Hsp70 contributes to the binding of Bag-1L to {tau}5 and to the regulation of the transactivation function of the androgen receptor. Chromatin immunoprecipitation studies demonstrated that the androgen receptor, Hsp70, and Bag-1L are all targeted to the androgen response elements of the gene that encodes prostate-specific antigen. These studies demonstrate the regulation of transcriptional activity of androgen receptor by a molecular chaperone-cochaperone complex.

* Corresponding author. Mailing address: Forschungszentrum Karlsruhe, Institute of Toxicology and Genetics, P.O. Box 3640, D-76021 Karlsruhe, Germany. Phone: 49 7247 822146. Fax: 49 7247 823354. E-mail: andrew.cato{at}itg.fzk.de.

Molecular and Cellular Biology, October 2003, p. 7189-7197, Vol. 23, No. 20
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.20.7189-7197.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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