PLK1 and β-TrCP-dependent ubiquitination and degradation of Rap1GAP controls cell proliferation

Dejie Wang, Pingzhao Zhang, Kun Gao, Yan Tang, Xiaofeng Jin, Yuanyuan Zhang, Qing Yi, Chenji Wang, Long Yu

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Rap1GAP is a GTPase-activating protein (GAP) that specifically stimulates the GTP hydrolysis of Rap1 GTPase. Although Rap1GAP is recognized as a tumor suppressor gene and downregulated in various cancers, little is known regarding the regulation of Rap1GAP ubiquitination and degradation under physiological conditions. Here, we demonstrated that Rap1GAP is ubiquitinated and degraded through proteasome pathway in mitosis. Proteolysis of Rap1GAP requires the PLK1 kinase and β-TrCP ubiquitin ligase complex. We revealed that PLK1 interacts with Rap1GAP in vivo through recognition of an SSP motif within Rap1GAP. PLK1 phosphorylates Ser525 in conserved 524DSGHVS529 degron of Rap1GAP and promotes its interaction with β-TrCP. We also showed that Rap1GAP was a cell cycle regulator and that tight regulation of the Rap1GAP degradation in mitosis is required for cell proliferation.

Original languageEnglish (US)
Article numbere110296
JournalPLoS ONE
Volume9
Issue number10
DOIs
StatePublished - Oct 17 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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