Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and   Sensitizes the Mitochondrial Apoptotic Pathway

doi:10.1074/jbc.M115.706341

CORC > 北京大学 > 化学与分子工程学院

	Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway
	Yun, Tao ; Yu, Kaiwen ; Yang, ShuangShuang ; Cui, Yifan ; Wang, Zixi ; Ren, Huiyu ; Chen, She ; Li, Lin ; Liu, Xiaoyun ; Fang, Min ; Jiang, Xuejun
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2016
关键词	HISTONE DEACETYLASE INHIBITORS CYTOCHROME-C TRANSCRIPTIONAL TARGET CELL-DEATH CANCER-CELLS BINDING ACTIVATION INDUCTION RELEASE PROCASPASE-9
DOI	10.1074/jbc.M115.706341
英文摘要	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.; National Basic Program of China 973 Program [2013CB910104]; National Science Foundation of China [31271524]; Peking University; National Institutes of Health [R01CA166413, R01GM113013]; Memorial Sloan Kettering Cancer Center [P30 CA008748]; SCI(E); EI; PubMed; ARTICLE; xiaoyun.liu@pku.edu.cn; min.fang@pku.edu.cn; jiangx@mskcc.org; 14; 7386-7395; 291
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/435035]
专题	化学与分子工程学院生命科学学院
推荐引用方式 GB/T 7714	Yun, Tao,Yu, Kaiwen,Yang, ShuangShuang,et al. Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2016.
APA	Yun, Tao.,Yu, Kaiwen.,Yang, ShuangShuang.,Cui, Yifan.,Wang, Zixi.,...&Jiang, Xuejun.(2016).Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway.JOURNAL OF BIOLOGICAL CHEMISTRY.
MLA	Yun, Tao,et al."Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway".JOURNAL OF BIOLOGICAL CHEMISTRY (2016).