MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity

Xingcheng Chen, Yuanhong Chen, Jixin Dong

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1826-1832
Number of pages7
JournalCellular Signalling
Volume28
Issue number12
DOIs
StatePublished - Dec 1 2016

Fingerprint

Mitosis
Serine
Phosphotransferases
Phosphorylation
Neoplasms
Carcinogenesis
CDC2 Protein Kinase
Antimitotic Agents
G2 Phase
Cell Division
Cell Proliferation
Growth
In Vitro Techniques

Keywords

  • CDK1
  • MST2
  • Mitotic phosphorylation
  • Tumor suppressor

ASJC Scopus subject areas

  • Cell Biology

Cite this

MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity. / Chen, Xingcheng; Chen, Yuanhong; Dong, Jixin.

In: Cellular Signalling, Vol. 28, No. 12, 01.12.2016, p. 1826-1832.

Research output: Contribution to journalArticle

Chen, Xingcheng ; Chen, Yuanhong ; Dong, Jixin. / MST2 phosphorylation at serine 385 in mitosis inhibits its tumor suppressing activity. In: Cellular Signalling. 2016 ; Vol. 28, No. 12. pp. 1826-1832.
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