p53CSV, a novel p53-inducible gene involved in the p53-dependent cell-survival pathway.
Although a number of p53 target genes have been identified, the mechanisms of p53-dependent activities that determine cellular survival or death are still not fully understood. Here we report isolation of a novel p53 target gene, designated p53-inducible cell-survival factor (p53CSV). p53CSV contains a p53-binding site within its second exon and the reduction of expression by small interfering RNA enhanced apoptosis, whereas overexpression protected cells from apoptosis caused by DNA damage. p53CSV is induced significantly when cells have a low level of genotoxic stresses, but not when DNA damage is severe. p53CSV can modulate apoptotic pathways through interaction with Hsp70 that probably inhibits activity of apoptosis protease activating factor-1. Our results imply that under specific conditions of stress, p53 regulates transcription of p53CSV and that p53CSV is one of the important players in the p53-mediated cell survival.
Park
Woong-Ryeon
WR
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Nakamura
Yusuke
Y
D000595:Amino Acid Sequence; D053477:Apoptotic Protease-Activating Factor 1; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D004249:DNA Damage / Q000235:genetics; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D045325:HCT116 Cells; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D011506:Proteins / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
C506592:APAF1 protein, human; D053477:Apoptotic Protease-Activating Factor 1; D061945:Caspase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C498536:TRIAP1 protein, human; D016159:Tumor Suppressor Protein p53; C506433:CASP9 protein, human; D053453:Caspase 9; D020169:Caspases