丝氨酸/苏氨酸蛋白磷酸酶与DNA损伤应答

DNA损伤应答(DNA damage response,DDR)是维持基因组稳定性的核心机制,对DDR的研究不仅有助于阐明癌症发生发展的机理,同时也为癌症治疗和抗癌新药开发提供生物学基础。蛋白质翻译后修饰,尤其是蛋白激酶介导的磷酸化修饰和蛋白磷酸酶介导的去磷酸化修饰,参与调控绝大多数的生命活动过程,包括DDR。对蛋白激酶ATM/ATR/CHK2/CHK1介导的DDR的研究已经比较透彻,但是对蛋白磷酸酶在DDR中的功能研究还有待加强和深入。比较全面地综述丝氨酸/苏氨酸蛋白磷酸酶在DDR中的功能并探讨在抗癌新药开发中的前景。

Serine/threonine protein phosphatases in DNA damage response

DNA damage response （DDR） is the essential mechanism for maintaining genome stability. Molecular dissection of DDR facilitates to understand the processes of cancer initiation and progression and to provide biological foundation for cancer therapy and cancer drug development. Protein post-translational modifications,particularly protein kinase-mediated phosphorylation and protein phosphatase-mediated dephosphorylation, are involved in regulating most, if not all, the biological processes, including DDR. The kinases ATM/ATR/CHK2/ CHKl-mediated DDR has been extensively investigated, however, many facets of protein phosphatases in DDR are awaiting to explore and uncover. This review comprehensively summarizes recent progress of serine/threonine protein phosphatases in DDR and discusses its potential application in cancer drug development.