Oncoprotein YAP regulates the spindle checkpoint activation in a mitotic phosphorylation-dependent manner through up-regulation of BubR1

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The transcriptional co-activator YAP (Yes-associated protein) functions as an oncogene; however, it is largely unclear how YAP exerts its oncogenic role. In this study, we further explored the functional significance of YAP and its mitotic phosphorylation in the spindle checkpoint. We found that the dynamic mitotic phosphorylation of YAP was CDC14-dependent. We also showed that YAP was required for the spindle checkpoint activation induced by spindle poisons. Mitotic phosphorylation of YAP was required for activation of the spindle checkpoint. Furthermore, enhanced expression of active YAP hyperactivated the spindle checkpoint and induced mitotic defects in a mitotic phosphorylation-dependent manner. Mechanistically, we documented that mitotic phosphorylation of YAP controlled transcription of genes associated with the spindle checkpoint. YAP constitutively associated with BubR1 (BUB1-related protein kinase), and knockdown of BubR1 relieved YAP-driven hyperactivation of the spindle checkpoint. Finally, we demonstrated that YAP promoted epithelial cell invasion via both mitotic phosphorylation and BubR1-dependent mechanisms. Together, our results reveal a novel link between YAP and the spindle checkpoint and indicate a potential mechanism underlying the oncogenic function of YAP through dysregulation of the spindle checkpoint.

Original languageEnglish (US)
Pages (from-to)6191-6202
Number of pages12
JournalJournal of Biological Chemistry
Volume290
Issue number10
DOIs
StatePublished - Mar 6 2015

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Phosphorylation
Oncogene Proteins
Up-Regulation
Chemical activation
Proteins
M Phase Cell Cycle Checkpoints
Poisons
Transcription
Oncogenes
Protein Kinases

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Oncoprotein YAP regulates the spindle checkpoint activation in a mitotic phosphorylation-dependent manner through up-regulation of BubR1. / Yang, Shuping; Zhang, Lin; Chen, Xingcheng; Chen, Yuanhong; Dong, Jixin.

In: Journal of Biological Chemistry, Vol. 290, No. 10, 06.03.2015, p. 6191-6202.

Research output: Contribution to journalArticle

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AU - Dong, Jixin

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