The CXXC finger 5 protein is required for DNA damage-induced p53 activation  

作　　者：ZHANG Min1,WANG RuiPeng1,WANG YanYi 2,DIAO FeiCi1,LU Fei1,GAO Dong1,CHEN DanYing 1,ZHAI ZhongHe1 & SHU HongBing2 1 College of Life Sciences,Peking University,Beijing 100871,China 2 College of Life Sciences,Wuhan University,Wuhan 430072,China 

出　　处：《Science China(Life Sciences)》2009年第6期528-538,共11页中国科学（生命科学英文版）

基　　金：Supported by National Basic Research Program of China (Grant No. 2006CB504301);National High Technology Research and Development Program of China (Grant No. 2006AA02A306);National Natural Science Foundation of China (Grant Nos. 30630019 and 30570959)

摘　　要：The tumor suppressor p53 is a critical component of the DNA damage response pathway that induces a set of genes responsible for cell cycle arrest,senescence,apoptosis,and DNA repair.The ataxia te-langiectasia mutated protein kinase(ATM) responds to DNA-damage stimuli and signals p53 stabiliza-tion and activation,thereby facilitating transactivation of p53 inducible genes and maintainence of genome integrity.In this study,we identified a CXXC zinc finger domain containing protein termed CF5 as a critical component in the DNA damage signaling pathway.CF5 induces p53 transcriptional activity and apoptosis in cells expressing wild type p53 but not in p53-deficient cells.Knockdown of CF5 in-hibits DNA damage-induced p53 activation as well as cell cycle arrest.Furthermore,CF5 physically interacts with ATM and is required for DNA damage-induced ATM phosphorylation but not its recruitment to chromatin.These findings suggest that CF5 plays a crucial role in ATM-p53 signaling in response to DNA damage.The tumor suppressor p53 is a critical component of the DNA damage response pathway that induces a set of genes responsible for cell cycle arrest,senescence,apoptosis,and DNA repair.The ataxia te-langiectasia mutated protein kinase(ATM) responds to DNA-damage stimuli and signals p53 stabiliza-tion and activation,thereby facilitating transactivation of p53 inducible genes and maintainence of genome integrity.In this study,we identified a CXXC zinc finger domain containing protein termed CF5 as a critical component in the DNA damage signaling pathway.CF5 induces p53 transcriptional activity and apoptosis in cells expressing wild type p53 but not in p53-deficient cells.Knockdown of CF5 in-hibits DNA damage-induced p53 activation as well as cell cycle arrest.Furthermore,CF5 physically interacts with ATM and is required for DNA damage-induced ATM phosphorylation but not its recruitment to chromatin.These findings suggest that CF5 plays a crucial role in ATM-p53 signaling in response to DNA damage.

关 键 词：P53 ATM DNA damage APOPTOSIS 

分 类 号：Q343[生物学—遗传学]