Deacetylation of the tumor suppressor protein PML regulates hydrogen peroxide-Induced cell death

D. Guan, J. H. Lim, L. Peng, Y. Liu, M. Lam, E. Seto, H. Y. Kao

研究成果: Article同行評審

37 引文 斯高帕斯(Scopus)

摘要

The promyelocytic leukemia protein (PML) is a tumor suppressor that is expressed at a low level in various cancers. Although post-Translational modifications including SUMOylation, phosphorylation, and ubiquitination have been found to regulate thestability or activity of PML, little is known about the role of its acetylation in the control of cell survival. Here we demonstrate that acetylation of lysine 487 (K487) and SUMO1 conjugation of K490 at PML protein are mutually exclusive. We found that hydrogen peroxide (H 2O2) promotes PML deacetylation and identified SIRT1 and SIRT5 as PML deacetylases. Both SIRT1 and SIRT5 are required for H 2O2-Mediated deacetylation of PML and accumulation of nuclear PML protein in HeLa cells. Knockdown of SIRT1 reduces the number of H2O2-Induced PML-nuclear bodies (NBs) and increases the survival of HeLa cells. Ectopic expression of wild-Type PML but not the K487R mutant rescues H2O2-Induced cell death in SIRT1 knockdown cells. Furthermore, ectopic expression of wild-Type SIRT5 but not a catalytic defective mutant can also restore H2O2-Induced cell death in SIRT1 knockdown cells. Taken together, our findings reveal a novel regulatory mechanism in which SIRT1/SIRT5-Mediated PML deacetylation plays a role in the regulation of cancer cell survival.

原文English
文章編號e1340
期刊Cell Death and Disease
5
發行號7
DOIs
出版狀態Published - 2014 7月

All Science Journal Classification (ASJC) codes

  • 免疫學
  • 細胞與分子神經科學
  • 細胞生物學
  • 癌症研究

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