Mechanistic insights into maintenance of high p53 acetylation by PTEN.
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-independent 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.
Li
Andrew G
AG
Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
Piluso
Landon G
LG
Cai
Xin
X
Wei
Gang
G
Sellers
William R
WR
Liu
Xuan
X
D000107:Acetylation; D002467:Cell Nucleus / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D013816:Thermodynamics; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
D046912:Multiprotein Complexes; D049790:Nuclear Export Signals; D019913:Nuclear Localization Signals; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D010749:Phosphoprotein Phosphatases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human