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PTEN Acetylation Modulates Its Interaction with PDZ Domain

¹ Life Sciences Institute and ² Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan and ³ Department of Pharmacology and the Moores Cancer Center, University of California at San Diego, La Jolla, California

Requests for reprints: Kun-Liang Guan, Department of Pharmacology and the Moores Cancer Center, University of California at San Diego, La Jolla, CA 92093-0815. Phone: 858-822-7945; Fax: 858-534-7638; E-mail: kuguan{at}ucsd.edu.

Key Words: PTEN • acetylation • PDZ domain

The PTEN tumor suppressor gene is frequently inactivated in human cancer. As a major tumor suppressor, PTEN function must be tightly regulated. Both phosphorylation and membrane association have been reported to regulate PTEN activity. In addition, the COOH terminus of PTEN has a typical PDZ domain-binding motif that interacts with several PDZ domain-containing proteins. In this report, we show that PTEN is acetylated on Lys⁴⁰², which is in the COOH-terminal PDZ domain-binding motif. We show that CBP plays a major role in PTEN acetylation, whereas the SIRT1 deacetylase is mainly responsible for PTEN deacetylation. Interestingly, Lys⁴⁰² acetylation modulates PTEN interaction with PDZ domain-containing proteins, indicating a potential role of acetylation in regulating PTEN function. [Cancer Res 2008;68(17):6908–12]