Department of Biotechnology, University of Kashmir, Srinagar, India.
Department of Biochemistry, University of Kashmir, Srinagar, India.
Mol Cell Biol. 2020 Apr 28;40(10). doi: 10.1128/MCB.00366-18.
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.
微管相关丝氨酸/苏氨酸激酶样（MASTL），也称为壁蛋白激酶（Gwl）激酶，在调节有丝分裂中起着重要作用。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，即细胞周期蛋白依赖性激酶 1（CDK1）方面起着至关重要的作用。已经观察到 MASTL 在各种类型的癌症中上调，并且还涉及肿瘤复发。它通过在激活/T 环中的磷酸化被 CDK1 激活，但它的完全激活机制仍不清楚。在这里，我们报告 AKT 在残基 T299 处磷酸化 MASTL，这在其激活中起着关键作用。我们的结果表明，AKT 增加 CDK1 介导的磷酸化，从而增加 MASTL 的活性，MASTL 通过抑制 PP2A 来促进有丝分裂进程。我们还表明，通过激活 MASTL 增强 AKT 的致癌潜力，因为抑制和/或沉默 MASTL 可以减弱 AKT 介导的结肠直肠细胞系中的增殖。简而言之，我们报告 AKT 通过磷酸化和激活 MASTL 在哺乳动物细胞有丝分裂的进展中起着重要作用。
