CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity

Seth Stauffer, Yongji Zeng, Jiuli Zhou, Xingcheng Chen, Yuanhong Chen, Jixin Dong

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

PDZ-binding kinase (PBK) plays a major role in proliferation and in safeguarding mitotic fidelity in cancer cells. Frequently upregulated in many cancers, PBK drives tumorigenesis and metastasis. PBK has been shown to be phosphorylated in mitosis by cyclin-dependent kinase 1 (CDK1)/cyclin B, however, no studies have been done examining PBK mitotic phosphorylation in oncogenesis. Additionally to the previously identified Threonine-9 phosphorylation, we found that Threonine-24, Serine-32, and Serine-59 of PBK are also phosphorylated. PBK is phosphorylated in vitro and in cells by CDK1 during antimitotic drug-induced mitotic arrest and in normal mitosis. We demonstrated that mitotic phosphorylation of Threonine-9 is involved in cytokinesis. The non-phosphorylatable mutant PBK-T9A augments tumorigenesis to a greater extent than wild type PBK in breast cancer cells, suggesting that PBK mitotic phosphorylation inhibits its tumor promoting activity. The PBK-T9A mutant also transforms and increases the proliferation of immortalized breast epithelial cells. Collectively, this study reveals that CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalCellular Signalling
Volume39
DOIs
StatePublished - Nov 2017

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CDC2 Protein Kinase
Cytokinesis
Phosphorylation
Threonine
Carcinogenesis
Mitosis
Serine
PDZ-binding kinase
Cyclin B
Antimitotic Agents
Neoplasms
Breast

Keywords

  • CDK1
  • Cytokinesis
  • Mitotic phosphorylation
  • Oncogenesis
  • PBK

ASJC Scopus subject areas

  • Cell Biology

Cite this

CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity. / Stauffer, Seth; Zeng, Yongji; Zhou, Jiuli; Chen, Xingcheng; Chen, Yuanhong; Dong, Jixin.

In: Cellular Signalling, Vol. 39, 11.2017, p. 74-83.

Research output: Contribution to journalArticle

Stauffer, Seth ; Zeng, Yongji ; Zhou, Jiuli ; Chen, Xingcheng ; Chen, Yuanhong ; Dong, Jixin. / CDK1-mediated mitotic phosphorylation of PBK is involved in cytokinesis and inhibits its oncogenic activity. In: Cellular Signalling. 2017 ; Vol. 39. pp. 74-83.
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