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The G2-to-M transition from a phosphatase perspective: a new vision of the meiotic division

机译:从磷酸酶的角度来看G2-〜M转变:减数分裂划分的新视野

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Cell division is orchestrated by the phosphorylation and dephosphorylation of thousands of proteins. These post-translational modifications underlie the molecular cascades converging to the activation of the universal mitotic kinase, Cdk1, and entry into cell division. They also govern the structural events that sustain the mechanics of cell division. While the role of protein kinases in mitosis has been well documented by decades of investigations, little was known regarding the control of protein phosphatases until the recent years. However, the regulation of phosphatase activities is as essential as kinases in controlling the activation of Cdk1 to enter M-phase. The regulation and the function of phosphatases result from post-translational modifications but also from the combinatorial association between conserved catalytic subunits and regulatory subunits that drive their substrate specificity, their cellular localization and their activity. It now appears that sequential dephosphorylations orchestrated by a network of phosphatase activities trigger Cdk1 activation and then order the structural events necessary for the timely execution of cell division. This review discusses a series of recent works describing the important roles played by protein phosphatases for the proper regulation of meiotic division. Many breakthroughs in the field of cell cycle research came from studies on oocyte meiotic divisions. Indeed, the meiotic division shares most of the molecular regulators with mitosis. The natural arrests of oocytes in G2 and in M-phase, the giant size of these cells, the variety of model species allowing either biochemical or imaging as well as genetics approaches explain why the process of meiosis has served as an historical model to decipher signalling pathways involved in the G2-to-M transition. The review especially highlights how the phosphatase PP2A-B55δ critically orchestrates the timing of meiosis resumption in amphibian oocytes. By opposing the kinase PKA, PP2A-B55δ controls the release of the G2 arrest through the dephosphorylation of their substrate, Arpp19. Few hours later, the inhibition of PP2A-B55δ by Arpp19 releases its opposing kinase, Cdk1, and triggers M-phase. In coordination with a variety of phosphatases and kinases, the PP2A-B55δ/Arpp19 duo therefore emerges as the key effector of the G2-to-M transition.
机译:细胞分裂由磷酸化和数千种蛋白质的磷酸化和去磷酸化策划。这些翻译后修饰利于将通用丝分裂激酶,CDK1的激活的分子级联级联呈趋于进入细胞分裂。他们还管理维持细胞分裂机制的结构事件。虽然蛋白激酶在有丝分裂中的作用已经通过数十年的调查进行了很好的记录,但对于近年来,蛋白质磷酸酶的控制很少。然而,磷酸酶活性的调节在控制CDK1的激活时是激酶,以进入M相。磷酸酶的调节和功能由翻译后修饰产生,而且来自保守的催化亚基和调节亚基之间的组合协会,其驱动其基质特异性,其细胞定位及其活性。目前似乎由​​磷酸酶活性策划的顺序脱磷,触发CDK1激活,然后订购及时执行细胞分裂所需的结构事件。该评论讨论了一系列最近的作品,描述了蛋白质磷酸酶用于适当调节减数分裂划分的重要作用。细胞周期研究领域的许多突破来自卵母细胞减数分裂的研究。实际上,减数分裂分裂份数份数含有有丝分裂的分子调节剂。 G2和M相的卵母细胞的自然丧失,这些细胞的巨大尺寸,允许生物化学或成像以及遗传学方法的各种模型物种解释了为什么MeIosis的过程作为破译信号传输的历史模型。参与G2-to-M转变的途径。审查特别突出了磷酸酶PP2A-B55δ如何重点衡量两栖卵母细胞中减数分裂恢复的时序。通过与激酶PKA相对,PP2A-B55δ通过其基质的去磷酸化来控制G2停滞的释放,ARPP19。几个小时后,通过ARPP19抑制PP2A-B55δ释放其相对的激酶,CDK1和触发M相。因此,在与各种磷酸酶和激酶的协调中,PP2A-B55Δ/ ARPP19 DUO被出现为G2至-M转变的关键效应器。

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