Ikenoue Tsuneo, Inoki Ken, Zhao Bin, Guan Kun-Liang
Life Sciences Institute, University of Michigan, Ann Arbor, USA.
Cancer Res. 2008 Sep 1;68(17):6908-12. doi: 10.1158/0008-5472.CAN-08-1107.
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 Lys(402), 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, Lys(402) acetylation modulates PTEN interaction with PDZ domain-containing proteins, indicating a potential role of acetylation in regulating PTEN function.
PTEN肿瘤抑制基因在人类癌症中常常失活。作为一种主要的肿瘤抑制因子，PTEN的功能必须受到严格调控。据报道，磷酸化和膜结合都可调节PTEN的活性。此外，PTEN的COOH末端有一个典型的PDZ结构域结合基序，可与几种含PDZ结构域的蛋白质相互作用。在本报告中，我们表明PTEN在位于COOH末端PDZ结构域结合基序中的赖氨酸（Lys）402处发生乙酰化。我们发现CBP在PTEN乙酰化中起主要作用，而SIRT1脱乙酰酶主要负责PTEN的去乙酰化。有趣的是，赖氨酸（Lys）402乙酰化调节PTEN与含PDZ结构域蛋白质的相互作用，表明乙酰化在调节PTEN功能中具有潜在作用。
