Phospho-regulation of KIBRA by CDK1 and CDC14 phosphatase controls cell-cycle progression

Ming Ji, Shuping Yang, Yuanhong Chen, Ling Xiao, Lin Zhang, Jixin Dong

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

KIBRA (kidney- and brain-expressed protein) is a novel regulator of the Hippo pathway, which controls tissue growth and tumorigenesis by regulating both cell proliferation and apoptosis. In mammals, KIBRA is associated with memory performance. The physiological function and regulation of KIBRA in nonneuronal cells remain largely unclear. We reported recently that KIBRA is phosphorylated by the mitotic kinases Aurora-A and - B. In the present study,we have expanded our analysis of KIBRA's role in cell-cycle progression. We show that KIBRA is also phosphorylated by CDK1 (cyclin-dependent kinase 1) in response to spindle damage stress. We have identified KIBRA Ser542 and Ser931 as main phosphorylation sites for CDK1 both in vitro and in vivo. Moreover, we found that the CDC (cell division cycle) 14A/B phosphatases associate with KIBRA, and CDK1-non-phosphorylatable KIBRA has greatly reduced interaction with CDC14B. CDC14A/B dephosphorylate CDK1-phosphorylated KIBRA in vitro and in cells. By using inducible-expression cell lines, we show further that phospho-regulation of KIBRA by CDK1 and CDC14 is involved in mitotic exit under spindle stress. Our results reveal a newmechanism through which KIBRA regulates cell-cycle progression.

Original languageEnglish (US)
Pages (from-to)93-102
Number of pages10
JournalBiochemical Journal
Volume447
Issue number1
DOIs
StatePublished - Oct 1 2012

Keywords

  • Cell division cycle 14A/B (CDC14A/B)
  • Cyclin-dependent kinase 1 (CDK1)
  • Hippo pathway
  • Kidney- and brain-expressed protein (KIBRA)
  • Mitosis
  • Phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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