This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ikenoue, T. Articles by Guan, K.-L. Search for Related Content PubMed PubMed Citation Articles by Ikenoue, T. Articles by Guan, K.-L.

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]