BIOLOGICAL SCIENCES / BIOCHEMISTRY

Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: A unique signaling pathway in the steroid receptor superfamily

Yi-Fen Lee, Chih-Rong Shyr, Tin Htwe Thin, Wen-Jye Lin, and Chawnshang Chang^*

George Whipple Lab for Cancer Research, Departments of Pathology, Urology, and Radiation Oncology, and The Cancer Center, University of Rochester Medical Center, Rochester, NY 14642

Accepted for publication November 4, 1999.

Received for publication September 9, 1999.

Abstract: The androgen receptor (AR) binds to androgen response elements and regulates target genes via a mechanism involving coregulators. Here we demonstrate that the AR can interact with the testicular orphan receptor-4 (TR4) and function as a repressor to down-regulate the TR4 target genes by preventing the TR4 binding to its target DNA. Interestingly, the heterodimerization of AR and TR4 also allows TR4 to repress AR target gene expression. Simultaneous exposure to both receptors therefore could result in bidirectional suppression of their target genes. Together, these data demonstrate that the coupling of two different receptors, through the heterodimerization of AR and TR4, is a unique signaling pathway in the steroid receptor superfamily, which may facilitate further understanding of the complicated androgen action in prostate cancer or libido.

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^* To whom reprint requests should be addressed. E-mail: chang{at}urmc.rochester.edu.

Communicated by Henry Lardy, University of Wisconsin, Madison, WI

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