AKT regulates mitotic progression of mammalian cells by phosphorylating MASTL

Abstract

Microtubule associated serine threonine like kinase (MASTL) has been recently identified as an important regulator 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 involved in tumor recurrence. It is activated by CDK1 through its auto regulatory loop but the complete mechanism of its activation is still unclear. In this study, we evaluated the regulation of MASTL via AKT during mitosis. Here we report that AKT phosphorylates MASTL at T299 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 cell proliferation.. We also show that the oncogenic potential of AKT is augmented by MASTL activation as the AKT mediated oncogenesis 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.

The MASTL/PP2A cell cycle kinase‐phosphatase module restrains PI3K‐Akt activity in an mTORC1‐dependent manner

“…It is, therefore, possible that MASTL may influence AKT signaling differentially in cycling (Vera et al , 2015) or starved/G0 cells as suggested by our data. Interestingly, AKT may lead to MASTL phosphorylation and activation specifically during mitosis (Reshi et al , 2020), although whether this is mediated by direct phosphorylation and whether these data have any relevance in vivo in a physiological context have not been addressed so far.…”

A cell cycle kinase-phosphatase module restrains PI3K-Akt activity in an mTORC1-dependent manner

“…It is therefore possible that MASTL may influence AKT signaling differentially in cycling 39 or starved/G0 cells as suggested by our data. Interestingly, AKT may lead to MASTL phosphorylation and activation specifically during mitosis 40 , although whether this is mediated by direct phosphorylation and whether these data have any relevance in vivo in a physiological context has not been addressed so far.…”