Wip1 (Wild-type p53-induced phosphatase1) is a member of PP2C (The type 2C family of protein phosphatases) family of phosphatases,which plays important roles in DNA damage repair and has attracted increasing attention as a oncogene.Wip1 knockout mice were viable,but exhibited reduced longevity,along with multiple-system abnormalities,including reproductive system,immune system,endocrine system and nervous system.The detailed phenotypes included male reproductive organ atrophy,male infertility,increased susceptibility to pathogens,diminished T-and B-cell function,insulin resistance,impaired body weight,declined fat mass,elevated anxiety-and depression-like behaviors and so on.The studies for the underlying molecular mechanisms further demonstrated that Wip 1 played critical roles in a variety of physiological and pathological processes through dephosphorylating different substrate proteins.Therefore,in this review,we comprehensively discussed the phenotypes caused by Wip 1 knockout in mouse as well as the possible underlying molecular mechanisms,which may provide information for further understanding the biological function of Wip 1,and the possible mechanisms underlying the physiological and pathological processes in mammals.%野生型p53诱导的磷酸酶1(Wild-type p53-induced phosphatase1,Wip1)是PP2C(The type 2C family of protein phosphatases)磷酸酶家族中的一员.在DNA损伤修复中起重要作用,并作为原癌基因受到越来越多的关注.Wip1敲除小鼠虽然能够存活,但寿命缩短,并出现多系统异常,包括生殖系统、免疫体系、内分泌系统、神经系统等,具体表现:雄性生殖器官萎缩及雄性不育、对病原体敏感、T细胞和B细胞功能受损、胰岛素抵抗、体重增长受限、脂肪量减少、焦虑和抑郁样行为增加等.相关机制研究发现,Wip1通过去磷酸化不同蛋白底物而在多种生理和病理过程中发挥重要作用.本文旨在对小鼠Wip1基因缺失所致表型及其初步的分子机制进行综述,为进一步研究Wip1的生物学功能以及哺乳动物体内生理和病理过程的发生机制提供参考.
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