Journal
CELLULAR SIGNALLING
Volume 28, Issue 12, Pages 1826-1832Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2016.08.013
Keywords
MST2; Mitotic phosphorylation; CDK1; Tumor suppressor
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Funding
- National Institutes of Health [P30 GM106397, R01 GM109066]
- Department of Defense Health Program [W81XWH-14-1-0150]
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Mammalian sterile 20-like kinase 1/2 (MST1/2) are core tumor suppressors in the Hippo signaling pathway. MST1/2 have been shown to regulate mitotic progression. Here, we report a novel mechanism for phospho-regulation of MST2 in mitosis and its biological significance in cancer. We found that the mitotic kinase cyclin-dependent kinase 1 (CDK1) phosphorylates MST2 in vitro and in vivo at serine 385 during antimitotic drug induced G2/M phase arrest. This phosphorylation occurs transiently during unperturbed mitosis. Mitotic phosphorylation of MST2 does not affect its kinase activity or Hippo-YAP signaling. We further showed that mitotic phosphorylation-deficient mutant MST2-S385A possesses higher activity in suppressing cell proliferation and anchorage-independent growth in vitro and tumorigenesis in vivo. Together, our findings reveal a novel layer of regulation for MST2 in mitosis and its role in tumorigenesis. (C) 2016 Elsevier Inc. All rights reserved.
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