Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies.
Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies.
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DOI：
10.1007/s11010-016-2693-2
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发表时间：
2016-05
影响因子：
4.3
通讯作者：
Agrawal DK
中科院分区：
文献类型：
--
作者：
Sur S;Agrawal DK
细胞周期调控基因的改变导致不受控制的细胞增殖，从而导致几种疾病。细胞周期蛋白依赖性激酶（CDK）及其调节亚基细胞周期蛋白是细胞周期进程中必不可少的蛋白。CDK的活性受一系列不同氨基酸残基的磷酸化和去磷酸化的调节。细胞分裂周期-25（CDC 25）通过去磷酸化和激活CDKs在细胞周期各相之间的转换中起重要作用。CDC 25 B和CDC 25 C在G2/M进展中起主要作用，而CDC 25 A有助于G1/S转换。不同异构体的CDC 25表达上调在各种临床病理情况。CDC 25 A的过表达使G1/S和G2/M事件（包括G2检查点）失调。CDC 25 B具有致癌特性。与14-3-3蛋白的结合调节CDC 25 B的活性和定位。CDC 25 C主要是哺乳动物细胞中的核蛋白。在G2/M转换时，CDC 25 C蛋白的有丝分裂活化通过其与14-3-3蛋白沿着其N-末端结构域内多个位点的磷酸化而发生。在这篇文章中，我们批判性地回顾了激酶/磷酸酶激活/失活的CDC 25的生物学，以维持CDK-cyclin的活性水平，从而基因组的稳定性，由于失调的CDC 25的临床意义和疾病中的潜在作用的CDC 25抑制剂。
Alterations in the cell cycle regulatory genes result in uncontrolled cell proliferation leading to several disease conditions. Cyclin-dependent kinases (CDK) and their regulatory subunit, cyclins, are essential proteins in cell-cycle progression. The activity of CDK is regulated by a series of phosphorylation and dephosphorylation at different amino acid residues. Cell Division Cycle-25 (CDC25) plays an important role in transitions between cell cycle phases by dephosphorylating and activating CDKs. CDC25B and CDC25C play a major role in G2/M progression, whereas CDC25A assists in G1/S transition. Different isomers of CDC25 expressions are upregulated in various clinicopathological situations. Overexpression of CDC25A deregulates G1/S and G2/M events, including the G2 checkpoint. CDC25B has oncogenic properties. Binding to the 14-3-3 proteins regulates the activity and localization of CDC25B. CDC25C is predominantly a nuclear protein in mammalian cells. At the G2/M transition, mitotic activation of CDC25C protein occurs by its dissociation from 14-3-3 proteins along with its phosphorylation at multiple sites within its N-terminal domain. In this article, we critically reviewed the biology of the activation/deactivation of CDC25 by kinases/phosphatases to maintain the level of CDK–cyclin activities and thus the genomic stability, clinical implications due to dysregulation of CDC25 and potential role of CDC25 inhibitors in diseases.