Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway
| Autor: | She Chen, Min Fang, Xiaoyun Liu, Tao Yun, Lin Li, Zixi Wang, Huiyu Ren, Kaiwen Yu, Yifan Cui, ShuangShuang Yang, Xuejun Jiang |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lysine Mutation Missense Apoptosis Histone Deacetylase 1 Butyrate Biochemistry 03 medical and health sciences 0302 clinical medicine Humans Molecular Biology Cell growth Chemistry Acetylation Cell Biology Transfection Molecular biology HDAC1 Mitochondria Up-Regulation Histone Deacetylase Inhibitors Apoptotic Protease-Activating Factor 1 030104 developmental biology Amino Acid Substitution 030220 oncology & carcinogenesis Histone deacetylase Tumor Suppressor Protein p53 HeLa Cells Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 291:7386-7395 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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