Nuclear localization of CDC25B1 and serine 146 integrity are required for induction of mitosis

Nuclear localization of CDC25B1 and serine 146 integrity are required for induction of mitosis
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DOI:
10.1074/jbc.m204430200
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发表时间:
2002-09-20
影响因子:
4.8
通讯作者:
Ducommun, B
Ducommun, B
中科院分区:
生物学2区
文献类型:
--
作者:
Baldin, V;Pelpel, K;Ducommun, B

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CDC25B磷酸酶是细胞有丝分裂过程中控制细胞周期蛋白依赖性蛋白激酶活性的重要调节因子。在这项研究中,我们证明了丝氨酸146是CDC25B1两个关键功能所必需的。CDC25B1作为有丝分裂的诱导剂和阻止CDC25B1从细胞核中排出是必不可少的。我们还发现丝氨酸146在体外可以被CDK1-Cyclin B磷酸化,但CDC25B的磷酸化不会刺激其磷酸酶活性,丝氨酸146的突变也不会影响其催化活性。丝氨酸146的磷酸化被认为是调控CDC25B功能的关键事件,CDC25B在哺乳动物有丝分裂的启动过程中发挥着重要作用。
CDC25B phosphatases are essential regulators that control cyclin-dependent kinases activities at the entry into mitosis. In this study, we demonstrate that serine 146 is required for two crucial features of CDC25B1. It is essential for CDC25B1 to function as a mitotic inducer and to prevent CDC25B1 export from the nucleus. We also show that serine 146 is phosphorylated in vitro by CDK1-cyclin B. However, phosphorylation of CDC25B does not stimulate its phosphatase activity, and mutation of serine 146 had no effect on its catalytic activity. Serine 146 phosphorylation is proposed to be a key event in the regulation of the CDC25B function in the initiation of mammalian mitosis.