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首页> 外文期刊>Cell cycle >MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.
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MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis.

机译：MASTL是长壁激酶的人类直系同源物，可促进有丝分裂进入，后期和胞质分裂。

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Greatwall (Gwl) was originally discovered in Drosophila as an essential kinase for correct chromosome condensation and mitotic progression. In Xenopus, Gwl may influence the positive-feedback loop that directs cyclin B1-Cdk1 activation and the mitotic state by inhibiting the phosphatase PP 2A. Here, we describe the human orthologue of Gwl called microtubule-associated serine/threonine kinase-like (MASTL). We found that MASTL localizes to the nucleus in interphase and re-localizes in part to centrosomes in mitosis, when it is active. Cells strongly depleted of MASTL by RNAi delay in G(2) phase and reveal slow chromosome condensation. MASTL RNAi cells that enter and progress through mitosis often fail to completely separate their sister chromatids in anaphase. This causes chromatin to be trapped in the cleavage furrow, which may lead to the formation of 4N G(1) cells by cytokinesis failure. Further, our experiments indicate that MASTL supports the phosphorylation state of mitotic phospho-proteins downstream of cyclin B1-Cdk1, including the APC/C. Cyclin B1 destruction is incomplete when mitotic cells that are strongly depleted of MASTL exit mitosis. We propose that MASTL enhances cyclin B1-Cdk1-dependent mitotic phosphorylation events, directing mitotic entry, anaphase and cytokinesis in human cells.
机译：长壁（Gwl）最初是在果蝇中发现的，它是正确染色体浓缩和有丝分裂进程的必需激酶。在非洲爪蟾中，Gwl可能会通过抑制磷酸酶PP 2A来影响正反馈环，该环会指导细胞周期蛋白B1-Cdk1激活和有丝分裂状态。在这里，我们描述了称为微管相关丝氨酸/苏氨酸激酶样（MASTL）的人类Gwl直系同源物。我们发现，当MASTL活跃时，它在相间定位于核，并在有丝分裂中部分重新定位于中心体。细胞被Gi（2）阶段的RNAi延迟严重耗尽MASTL，并显示出缓慢的染色体浓缩。进入有丝分裂并通过有丝分裂进展的MASTL RNAi细胞通常无法在后期完全分离其姐妹染色单体。这导致染色质被困在切割沟中，这可能会由于胞质分裂失败而导致4N G（1）细胞的形成。此外，我们的实验表明，MASTL支持细胞周期蛋白B1-Cdk1（包括APC / C）下游的有丝分裂磷酸蛋白的磷酸化状态。当强烈消耗MASTL的有丝分裂细胞退出有丝分裂时，细胞周期蛋白B1的破坏是不完全的。我们建议，MASTL增强细胞周期蛋白B1-Cdk1依赖的有丝分裂磷酸化事件，指导人类细胞中的有丝分裂进入，后期和胞质分裂。

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