1. APCCDH1 Targets MgcRacGAP for Destruction in the Late M Phase
- Author
-
Nishimura, Koutarou, Oki, Toshihiko, Kitaura, Jiro, Kuninaka, Shinji, Saya, Hideyuki, Sakaue-Sawano, Asako, Miyawaki, Atsushi, and Kitamura, Toshio
- Subjects
AMMONIUM perchlorate ,TARGETED drug delivery ,GERM cells ,GTPASE-activating protein ,RHO-associated kinases ,CYTOKINESIS ,CELL cycle - 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 APC
CDH1 . 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. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF