CDK1 phosphorylation of TAZ in mitosis inhibits its oncogenic activity

Lin Zhang, Xingcheng Chen, Seth Stauffer, Shuping Yang, Yuanhong Chen, Jixin Dong

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The transcriptional co-activator with PDZ-binding motif (TAZ) is a downstream effector of the Hippo tumor suppressor pathway, which plays important roles in cancer and stem cell biology. Hippo signaling inactivates TAZ through phosphorylation (mainly at S89). In the current study, we define a new layer of regulation of TAZ activity that is critical for its oncogenic function. We found that TAZ is phosphorylated in vitro and in vivo by the mitotic kinase CDK1 at S90, S105, T326, and T346 during the G2/M phase of the cell cycle. Interestingly, mitotic phosphorylation inactivates TAZ oncogenic activity, as the non-phosphorylatable mutant (TAZ-S89A/S90A/S105A/T326A/T346A, TAZ-5A) possesses higher activity in epithelial-mesenchymal transition, anchorage-independent growth, cell migration, and invasion when compared to the TAZ-S89A mutant. Accordingly, TAZ-5A has higher transcriptional activity compared to the TAZ-S89A mutant. Finally, we show that TAZ-S89A or TAZ-5A (to a greater extent) was sufficient to induce spindle and centrosome defects, and chromosome misalignment/missegregation in immortalized epithelial cells. Together, our results reveal a previously unrecognized connection between TAZ oncogenicity and mitotic phospho-regulation.

Original languageEnglish (US)
Pages (from-to)31399-31412
Number of pages14
JournalOncotarget
Volume6
Issue number31
DOIs
StatePublished - Jan 1 2015

Fingerprint

Mitosis
Phosphorylation
Centrosome
Epithelial-Mesenchymal Transition
Neoplastic Stem Cells
G2 Phase
Cell Division
Cell Movement
Cell Biology
Cell Cycle
Phosphotransferases
Chromosomes
Epithelial Cells
Growth
Neoplasms
In Vitro Techniques

Keywords

  • CDK1
  • Hippo pathway
  • Mitotic defects
  • Mitotic phosphorylation
  • TAZ

ASJC Scopus subject areas

  • Oncology

Cite this

CDK1 phosphorylation of TAZ in mitosis inhibits its oncogenic activity. / Zhang, Lin; Chen, Xingcheng; Stauffer, Seth; Yang, Shuping; Chen, Yuanhong; Dong, Jixin.

In: Oncotarget, Vol. 6, No. 31, 01.01.2015, p. 31399-31412.

Research output: Contribution to journalArticle

Zhang, L, Chen, X, Stauffer, S, Yang, S, Chen, Y & Dong, J 2015, 'CDK1 phosphorylation of TAZ in mitosis inhibits its oncogenic activity', Oncotarget, vol. 6, no. 31, pp. 31399-31412. https://doi.org/10.18632/oncotarget.5189
Zhang, Lin ; Chen, Xingcheng ; Stauffer, Seth ; Yang, Shuping ; Chen, Yuanhong ; Dong, Jixin. / CDK1 phosphorylation of TAZ in mitosis inhibits its oncogenic activity. In: Oncotarget. 2015 ; Vol. 6, No. 31. pp. 31399-31412.
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