Mechanistic insights into maintenance of high p53 acetylation by PTEN

被引:146
作者
Li, Andrew G.
Piluso, Landon G.
Cai, Xin
Wei, Gang
Sellers, William R.
Liu, Xuan [1 ]
机构
[1] Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA
[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
关键词
D O I
10.1016/j.molcel.2006.06.028
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Earlier studies have shown that PTEN regulated p53 protein stability both in a phosphatase-dependent manner through antagonizing Akt-Mdm2 pathway and in a phosphatase-in dependent manner through interacting with p53. In this study, we report that PTEN forms a complex with p300 in the nucleus and plays a role in maintenance of high p53 acetylation in response to DNA damage. Furthermore, p300 is required for nuclear PTEN-regulated cell cycle arrest. Interestingly, however, p53 acetylation was found to promote PTEN-p53 interaction. To investigate the molecular mechanisms, we show that acetylation promotes p53 tetramerization, which, in turn, is required for the PTEN-p53 interaction and subsequent maintenance of high p53 acetylation. Taken together, our results suggest a physiological role for the PTEN tumor suppressor in the nucleus and provide a molecular explanation for our previous observation that PTEN controls p53 protein levels independent of its phosphatase activity.
引用
收藏
页码:575 / 587
页数:13
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