AKT regulates mitotic progression of mammalian cells by phosphorylating MASTL leading to PP2A inactivation.

Microtubule associated serine threonine like kinase (MASTL), also known as Greatwall kinase (Gwl), has an important role in the regulation of mitosis. By inhibiting protein phosphatase 2A, it plays a crucial role in activating one of the most important mitotic kinases known as cyclin dependent kinase1 (CDK1). MASTL has been seen to be up regulated 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 T299 residue which plays a critical role in its activation. Our results suggest that AKT increases CDK1 mediated phosphorylation and hence 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 as the AKT mediated proliferation in colorectal cell lines can be attenuated by inhibiting and/or silencing MASTL. In brief, we report that AKT has an important role in the progression of mitosis in mammalian cells and it does so through the phosphorylation and activation of MASTL.