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AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation.
Mol Cell Biol. 2020 04 28; 40(10)MC

Abstract

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.

Authors+Show Affiliations

Department of Biotechnology, University of Kashmir, Srinagar, India.Department of Biochemistry, University of Kashmir, Srinagar, India.Department of Biotechnology, University of Kashmir, Srinagar, India.Department of Biochemistry, University of Kashmir, Srinagar, India.Department of Biotechnology, University of Kashmir, Srinagar, India.Department of Biochemistry, University of Kashmir, Srinagar, India.Department of Biochemistry, University of Kashmir, Srinagar, India.Department of Biotechnology, University of Kashmir, Srinagar, India.Department of Biochemistry, University of Kashmir, Srinagar, India shaida.andrabi@uok.edu.in.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32123010

Citation

Reshi, Irfana, et al. "AKT Regulates Mitotic Progression of Mammalian Cells By Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation." Molecular and Cellular Biology, vol. 40, no. 10, 2020.
Reshi I, Nisa MU, Farooq U, et al. AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation. Mol Cell Biol. 2020;40(10).
Reshi, I., Nisa, M. U., Farooq, U., Gillani, S. Q., Bhat, S. A., Sarwar, Z., Nabi, N., Fazili, K. M., & Andrabi, S. (2020). AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation. Molecular and Cellular Biology, 40(10). https://doi.org/10.1128/MCB.00366-18
Reshi I, et al. AKT Regulates Mitotic Progression of Mammalian Cells By Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation. Mol Cell Biol. 2020 04 28;40(10) PubMed PMID: 32123010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AKT Regulates Mitotic Progression of Mammalian Cells by Phosphorylating MASTL, Leading to Protein Phosphatase 2A Inactivation. AU - Reshi,Irfana, AU - Nisa,Misbah Un, AU - Farooq,Umer, AU - Gillani,Syed Qaaifah, AU - Bhat,Sameer Ahmed, AU - Sarwar,Zarka, AU - Nabi,Nusrat, AU - Fazili,Khalid Majid, AU - Andrabi,Shaida, Y1 - 2020/04/28/ PY - 2018/07/20/received PY - 2020/02/25/accepted PY - 2020/10/28/pmc-release PY - 2020/3/4/pubmed PY - 2020/8/12/medline PY - 2020/3/4/entrez KW - Akt KW - Greatwall kinase KW - MASTL KW - PP2A KW - cancer KW - mitosis JF - Molecular and cellular biology JO - Mol. Cell. Biol. VL - 40 IS - 10 N2 - 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. SN - 1098-5549 UR - https://www.unboundmedicine.com/medline/citation/32123010/AKT_Regulates_Mitotic_Progression_of_Mammalian_Cells_by_Phosphorylating_MASTL_Leading_to_Protein_Phosphatase_2A_Inactivation_ L2 - http://mcb.asm.org/cgi/pmidlookup?view=long&pmid=32123010 DB - PRIME DP - Unbound Medicine ER -