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

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Abstract

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 telangiectasia mutated protein kinase (ATM) responds to DNA-damage stimuli and signals p53 stabilization 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 inhibits 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.

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Authors and Affiliations

  1. College of Life Sciences, Peking University, Beijing, 100871, China

    Min Zhang, RuiPeng Wang, FeiCi Diao, Fei Lu, Dong Gao, DanYing Chen & ZhongHe Zhai

  2. College of Life Sciences, Wuhan University, Wuhan, 430072, China

    YanYi Wang & HongBing Shu

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  1. Min Zhang
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  2. RuiPeng Wang
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Correspondence to HongBing Shu.

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

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Zhang, M., Wang, R., Wang, Y. et al. The CXXC finger 5 protein is required for DNA damage-induced p53 activation. SCI CHINA SER C 52, 528–538 (2009). https://doi.org/10.1007/s11427-009-0083-7

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