RT Journal Article
SR Electronic
T1 AKT regulates mitotic progression of mammalian cells by phosphorylating MASTL
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 375618
DO 10.1101/375618
A1 Irfana Reshi
A1 Misbah Un Nisa
A1 Umer Farooq
A1 Syed Qaaifah Gillani
A1 Sameer Ahmad Bhat
A1 Zarka Sarwar
A1 Khalid Majid Fazili
A1 Shaida Andrabi
YR 2018
UL http://biorxiv.org/content/early/2018/07/24/375618.abstract
AB 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.