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.
authors: From the Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Division of Cell Biology, School of Life Sciences, the Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065.
authors: Tao
authors: T
authors: Yun
authors: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, and.
authors: Kaiwen
authors: K
authors: Yu
authors: State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Yiheyuan Avenue 5, Haidian District, Beijing 100875, China.
authors: ShuangShuang
authors: S
authors: Yang
authors: From the Peking-Tsinghua Center for Life Sciences, Division of Cell Biology, School of Life Sciences.
authors: Yifan
authors: Y
authors: Cui
authors: From the Peking-Tsinghua Center for Life Sciences, Division of Cell Biology, School of Life Sciences.
authors: Zixi
authors: Z
authors: Wang
authors: From the Peking-Tsinghua Center for Life Sciences, Division of Cell Biology, School of Life Sciences.
authors: Huiyu
authors: H
authors: Ren
authors: the National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China, and.
authors: She
authors: S
authors: Chen
authors: the National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China, and.
authors: Lin
authors: L
authors: Li
authors: Institute of Analytical Chemistry and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, and xiaoyun.liu@pku.edu.cn.
authors: Xiaoyun
authors: X
authors: Liu
authors: From the Peking-Tsinghua Center for Life Sciences, Division of Cell Biology, School of Life Sciences, min.fang@pku.edu.cn.
authors: Min
authors: M
authors: Fang
authors: the Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065 jiangx@mskcc.org.
authors: Xuejun
authors: X
authors: Jiang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D019943:Amino Acid Substitution; D017209:Apoptosis; D053477:Apoptotic Protease-Activating Factor 1 / Q000096:biosynthesis* / Q000235:genetics; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D056572:Histone Deacetylase Inhibitors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D008239:Lysine