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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

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.

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