Aressy Bernadette, Ducommun Bernard
University of Toulouse, CNRS-UMR5088 and IFR109 "Institut d'Exploration Fonctionnelle des Génomes", 118 route de Narbonne, 31062 TOULOUSE, France.
Anticancer Agents Med Chem. 2008 Dec;8(8):818-24. doi: 10.2174/187152008786847756.
Cell division cycle 25 (CDC25) phosphatases are key actors in eukaryotic cell cycle control. They are responsible for the dephosphorylations that activate the cyclin-dependent kinases (CDK) at specific stages of the cell cycle. Human CDC25A, CDC25B and CDC25C are also central targets and regulators of the G2/M checkpoint mechanisms activated in response to DNA injury. The expression and activity of these enzymes is finely regulated by multiple mechanisms including post-translational modifications, interactions with regulatory partners, control of their intracellular localization, and cell cycle-regulated degradation. Altered expression of these phosphatases is associated with checkpoint bypass and genetic instability. Accordingly, increased expression of CDC25A and CDC25B is found in many high-grade tumors and is correlated with poor prognosis in human cancers. This review summarizes our current knowledge within this domain and discusses the data that support therapeutic strategies targeting CDC25 activity in the treatment of cancer.
细胞分裂周期25（CDC25）磷酸酶是真核细胞周期调控中的关键因子。它们负责在细胞周期的特定阶段进行去磷酸化，从而激活细胞周期蛋白依赖性激酶（CDK）。人类CDC25A、CDC25B和CDC25C也是响应DNA损伤而激活的G2/M检查点机制的核心靶点和调节因子。这些酶的表达和活性受到多种机制的精细调控，包括翻译后修饰、与调节伙伴的相互作用、细胞内定位的控制以及细胞周期调控的降解。这些磷酸酶表达的改变与检查点绕过和基因不稳定有关。因此，在许多高级别肿瘤中发现CDC25A和CDC25B的表达增加，并且与人类癌症的不良预后相关。本综述总结了我们目前在该领域的知识，并讨论了支持针对CDC25活性的治疗策略用于癌症治疗的数据。
