Acetylation of p53 protein at lysine 120 up-regulates apaf-1 protein and sensitizes the mitochondrial apoptotic pathway

Tao Yun, Kaiwen Yu, Shuang Shuang Yan, Yifan Cui, Zixi Wang, Huiyu Ren, She Chen, Lin Li, Xiaoyun Liu, Min Fang, Xuejun Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

The p53 tumor suppressor controls cell growth, metabolism, and death by regulating the transcription of various target genes. The target-specific transcriptional activity of p53 is highly regulated. Here we demonstrate that acetylation of p53 at Lys-120 up-regulates its transcriptional activity toward Apaf-1, a core component in the mitochondrial apoptotic pathway, and thus sensitizes caspase activation and apoptosis. We found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild- Type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore,HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up-regulation of Apaf-1.

Original languageEnglish (US)
Pages (from-to)7386-7395
Number of pages10
JournalJournal of Biological Chemistry
Volume291
Issue number14
DOIs
StatePublished - Apr 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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