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Molecular and Cellular Biology, February 2004, p. 1044-1057, Vol. 24, No. 3
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.3.1044-1057.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

ARA67/PAT1 Functions as a Repressor To Suppress Androgen Receptor Transactivation

Yanqing Zhang, Yue Yang, Shuyuan Yeh, and Chawnshang Chang*

Departments of Pathology, Urology, and Radiation Oncology and Cancer Center, George Whipple Laboratory for Cancer Research, University of Rochester Medical Center, Rochester, New York 14642

Received 14 April 2003/ Returned for modification 16 June 2003/ Accepted 6 November 2003

The androgen receptor (AR) may recruit multiple coregulators for proper or optimal transactivation. Here we report the identification and characterization of ARA67/PAT1 as an AR coregulator from a prostate cDNA library. ARA67/PAT1 was screened out as an AR N terminus interacting protein. Interaction mapping shows that the cooperation of multiple domains within ARA67/PAT1 may be required for the maximal interaction with AR. ARA67/PAT1 functions as a repressor with better suppressive effects on AR compared to glucocorticoid receptor and estrogen receptor. Further mechanism dissection reveals that the interrupted AR cytoplasmic-nuclear shuttling may play a major role in ARA67/PAT1 mediated suppression on AR. Together, these results suggest that ARA67/PAT1 may function as a novel repressor that can modulate AR function in prostate cancer.

* Corresponding author. Mailing address: George Whipple Laboratory for Cancer Research, University of Rochester Medical Center, 601 Elmwood Ave., Box 626, Rochester, NY 14642. Phone: (585) 275-9994. Fax: (585) 756-4133. E-mail: chang{at}URMC.rochester.edu. {dagger} Present address: Department of Surgery, First Hospital, Peking University, Beijing, People’s Republic of China.

Molecular and Cellular Biology, February 2004, p. 1044-1057, Vol. 24, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.3.1044-1057.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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