APCCDH1 Targets MgcRacGAP for Destruction in the Late M Phase

Koutarou Nishimura, Toshihiko Oki, Jiro Kitaura, Shinji Kuninaka, Hideyuki Saya, Asako Sakaue-Sawano, Atsushi Miyawaki, Toshio Kitamura

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11 Citations (Scopus)

Abstract

Background:Male germ cell RacGTPase activating protein (MgcRacGAP) is an important regulator of the Rho family GTPases - RhoA, Rac1, and Cdc42 - and is indispensable in cytokinesis and cell cycle progression. Inactivation of RhoA by phosphorylated MgcRacGAP is an essential step in cytokinesis. MgcRacGAP is also involved in G1-S transition and nuclear transport of signal transducer and activator of transcription 3/5 (STAT3/5). Expression of MgcRacGAP is strictly controlled in a cell cycle-dependent manner. However, the underlying mechanisms have not been elucidated.Methodology/Principal Findings:Using MgcRacGAP deletion mutants and the fusion proteins of full-length or partial fragments of MgcRacGAP to mVenus fluorescent protein, we demonstrated that MgcRacGAP is degraded by the ubiquitin-proteasome pathway in the late M to G1 phase via APCCDH1. We also identified the critical region for destruction located in the C-terminus of MgcRacGAP, AA537-570, which is necessary and sufficient for CDH1-mediated MgcRacGAP destruction. In addition, we identified a PEST domain-like structure with charged residues in MgcRacGAP and implicate it in effective ubiquitination of MgcRacGAP.Conclusions/Significance:Our findings not only reveal a novel mechanism for controlling the expression level of MgcRacGAP but also identify a new target of APCCDH1. Moreover our results identify a C-terminal region AA537-570 of MgcRacGAP as its degron.

Original languageEnglish
Article numbere63001
JournalPloS one
Volume8
Issue number5
DOIs
Publication statusPublished - 2013 May 16

ASJC Scopus subject areas

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

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    Nishimura, K., Oki, T., Kitaura, J., Kuninaka, S., Saya, H., Sakaue-Sawano, A., Miyawaki, A., & Kitamura, T. (2013). APCCDH1 Targets MgcRacGAP for Destruction in the Late M Phase. PloS one, 8(5), [e63001]. https://doi.org/10.1371/journal.pone.0063001