Open AccessAKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation
Author(s) -
Irfana Reshi,
Misbah Un Nisa,
Umer Farooq,
Syed Qaaifah Gillani,
Sameer Ahmed Bhat,
Zarka Sarwar,
Nusrat Nabi,
Khalid Majid Fazili,
Shaida Andrabi
Publication year - 2020
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00366-18
Subject(s) - protein kinase b , mitosis , protein phosphatase 2 , cyclin dependent kinase 1 , phosphorylation , microbiology and biotechnology , biology , kinase , phosphatase , dephosphorylation , pi3k/akt/mtor pathway , cell cycle , cancer research , signal transduction , biochemistry , cell
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.