Journal of Biological Chemistry
Volume 277, Issue 44, 1 November 2002, Pages 41311-41317
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PROTEIN SYNTHESIS POST-TRANSLATION MODIFICATION AND DEGRADATION
PIAS1 and PIASxα Function as SUMO-E3 Ligases toward Androgen Receptor and Repress Androgen Receptor-dependent Transcription*

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The androgen receptor (AR) has been shown to be modified by SUMO-1, a ubiquitin-like protein. Recently we showed that PIAS family proteins function as SUMO-E3 ligases. Here we provide evidence that PIAS1 and PIASxα act as specific SUMO-E3 ligases for the AR. PIAS1 and PIASxα but not PIAS3 or PIASxβ enhanced the sumoylation of AR in intact cells and in vitro. PIAS1 and PIASxα bound Ubc9, the E2 enzyme for SUMO-1, in a RING finger-like domain-dependent manner. Consistent with previous studies (Kahyo, T., Nishida, T., and Yasuda, H. (2001)Mol. Cell8, 713–718), the RING finger-like domain of the SUMO-E3 was required for ligase activity. The binding of a ligand, e.g. testosterone, to the AR was required for the sumoylation of AR in intact cells. Although AR-dependent transcription was enhanced by PIAS proteins without sumoylation of the receptor, PIAS1 and PIASxα repressed AR-dependent transcription in a manner dependent on the ectopic expression of SUMO-1 and their RING finger-like domain. Furthermore, the sumoylation sites of the AR were necessary for the full repressive effect on AR-dependent transactivation, indicating that the sumoylation of AR was crucial for the repression of transactivation of the AR. Thus, PIAS1 and PIASxα modulate the AR-dependent transactivation, which, at least in part, can be attributed to their SUMO-E3 activity toward AR.

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Published, JBC Papers in Press, August 9, 2002, DOI 10.1074/jbc.M206741200

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This work was supported in part by a grant-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and also by the Uehara Memorial Foundation (to H. Y.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.