Microtubule-associated serine/threonine kinase like (MASTL), also known as Greatwall (Gwl) kinase, has an important role in the regulation of mitosis. By inhibiting protein phosphatase 2A (PP2A), it plays a crucial role in activating one of the most important mitotic kinases, known as cyclin-dependent kinase 1 (CDK1). MASTL has been seen to be upregulated in various types of cancers and is also involved in tumor recurrence. It is activated by CDK1 through phosphorylations in the activation/T-loop, but the complete mechanism of its activation is still unclear. Here, we report that AKT phosphorylates MASTL at residue T299, which plays a critical role in its activation. Our results suggest that AKT increases CDK1-mediated phosphorylation and hence the activity of MASTL, which, in turn, promotes mitotic progression through PP2A inhibition. We also show that the oncogenic potential of AKT is augmented by MASTL activation, since AKT-mediated proliferation in colorectal cell lines can be attenuated by inhibiting and/or silencing MASTL. In brief, we report that AKT plays an important role in the progression of mitosis in mammalian cells and that it does so through the phosphorylation and activation of MASTL.

中文翻译：

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AKT通过磷酸化MASTL调节哺乳动物细胞的有丝分裂进程，导致蛋白磷酸酶2A失活。

微管相关的丝氨酸/苏氨酸激酶样（MASTL），也称为长壁（Gwl）激酶，在有丝分裂的调节中具有重要作用。通过抑制蛋白磷酸酶2A（PP2A），它在激活最重要的有丝分裂激酶之一中起着至关重要的作用，称为细胞周期蛋白依赖性激酶1（CDK1）。已经发现MASTL在各种类型的癌症中上调，并且还参与肿瘤复发。CDK1通过激活/ T环中的磷酸化将其激活，但其激活的完整机制仍不清楚。在这里，我们报告说AKT在残基T299上使MASTL磷酸化，该残基在其激活中起关键作用。我们的结果表明，AKT增加CDK1介导的磷酸化作用，并因此增加MASTL的活性，进而通过PP2A抑制促进有丝分裂进程。我们还显示，由于AKT介导的结直肠细胞系增殖可通过抑制和/或沉默MASTL来减弱，因此MASTL激活可增强AKT的致癌潜力。简而言之，我们报道AKT在哺乳动物细胞的有丝分裂进程中起着重要作用，并且它通过MASTL的磷酸化和激活来发挥作用。