MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity.
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.
Mesh Terms:
Animals, Antimitotic Agents, CDC2 Protein Kinase, Carcinogenesis, Cell Cycle Checkpoints, Cell Proliferation, Cyclin B, HEK293 Cells, HeLa Cells, Humans, Male, Mice, Nude, Mitosis, Mutant Proteins, Phosphorylation, Phosphoserine, Protein-Serine-Threonine Kinases, Signal Transduction, Tumor Suppressor Proteins
Animals, Antimitotic Agents, CDC2 Protein Kinase, Carcinogenesis, Cell Cycle Checkpoints, Cell Proliferation, Cyclin B, HEK293 Cells, HeLa Cells, Humans, Male, Mice, Nude, Mitosis, Mutant Proteins, Phosphorylation, Phosphoserine, Protein-Serine-Threonine Kinases, Signal Transduction, Tumor Suppressor Proteins
Cell. Signal.
Date: Dec. 01, 2015
PubMed ID: 27566175
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