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J. Biol. Chem., Vol. 281, Issue 31, 21848-21856, August 4, 2006

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Coordinated Regulation of AIB1 Transcriptional Activity by Sumoylation and Phosphorylation^*

From the Department of Biochemistry and Molecular Biology, Peking University Health Science Center, 38 Xue Yuan Road, Beijing 100083, China

AIB1, a member of the steroid receptor coactivator (SRC) family that participates in gene transcriptional activation by nuclear receptors and other transcription factors, is required for animal growth and reproductive development and implicated in breast carcinogenesis. The mechanisms underlying the AIB1 pleiotropic functions are not fully understood and neither is the regulation of its activity. Here, we showed that AIB1 was a sumoylated protein and the sumoylation attenuated the transactivation activity of AIB1, which is in contrast to the sumoylation of its paralogs, GRIP1 and SRC-1. The transactivation activity of AIB1 is enhanced by its phosphorylation by several kinases, including mitogen-activated protein kinase. We demonstrated in this report that estrogen treatment led to an increased phosphorylation and decreased sumoylation of AIB1 and that the sumoylation coordinated with phosphorylation in regulating the transcriptional activity of AIB1, providing a mechanism for post-translational modifications in regulating the transcriptional output of AIB1.

Received for publication, April 19, 2006 , and in revised form, June 5, 2006.

^* This work was supported by the National Natural Science Foundation of China (Grants 30225043, 30393110, and 30470912 to Y. S.) and by the Ministry of Science and Technology of China (863 Program Grant 2002BA711A01 and 973 Program Grant 2005CB522404 to Y. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed. Tel.: 86-10-8280-5118; Fax: 86-10-8280-1355; E-mail: yshang{at}hsc.pku.edu.cn.

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