title: APC(CDH1) targets MgcRacGAP for destruction in the late M phase.
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.
  
  
  RESULTS
  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
  Our findings not only reveal a novel mechanism for controlling the expression level of MgcRacGAP but also identify a new target of APC(CDH1). Moreover our results identify a C-terminal region AA537-570 of MgcRacGAP as its degron.
authors.affiliation: Division of Cellular Therapy, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan.
authors.forename: Koutarou
authors.initials: K
authors.lastname: Nishimura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Oki
authors.forename: Jiro
authors.initials: J
authors.lastname: Kitaura
authors.forename: Shinji
authors.initials: S
authors.lastname: Kuninaka
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Saya
authors.forename: Asako
authors.initials: A
authors.lastname: Sakaue-Sawano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyawaki
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D064200:Cdh1 Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002460:Cell Line; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D041681:NIH 3T3 Cells; D011485:Protein Binding; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000502:physiology
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D064200:Cdh1 Proteins; C577585:Fzr1 protein, mouse; D020690:GTPase-Activating Proteins; C115995:mgcRacGAP