Acetylation of p53 protein at lysine 120 up-regulates Apaf-1 protein and sensitizes the mitochondrial apoptotic pathway Journal Article
| Authors: | Yun, T.; Yu, K.; Yan, S. S.; Cui, Y.; Wang, Z.; Ren, H.; Chen, S.; Li, L.; Liu, X.; Fang, M.; Jiang, X. |
| Article Title: | Acetylation of p53 protein at lysine 120 up-regulates Apaf-1 protein and sensitizes the mitochondrial apoptotic pathway |
| 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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc. |
| Keywords: | proteins; cell death; transcription; amino acids; up-regulation; molecular biology; histone deacetylases; acetylation; caspase activation; tumor suppressors; transcriptional activity; hdac inhibitors; apoptotic pathways; core components |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 291 |
| Issue: | 14 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2016-04-01 |
| Start Page: | 7386 |
| End Page: | 7395 |
| Language: | English |
| DOI: | 10.1074/jbc.M115.706341 |
| PROVIDER: | scopus |
| PMCID: | PMC4817170 |
| PUBMED: | 26851285 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 June 2016 -- Source: Scopus |
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