Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins.
The anaphase-promoting complex/cyclosome (APC) ubiquitin ligase is activated by Cdc20 and Cdh1 and inhibited by Mad2 and the spindle assembly checkpoint complex, Mad2B, and the early mitotic inhibitor Emi1. Mad2 inhibits APC(Cdc20), whereas Mad2B preferentially inhibits APC(Cdh1). We have examined the mechanism of APC inhibition by Emi1 and find that unlike Mad2 proteins, Emi1 binds and inhibits both APC(Cdh1) and APC(Cdc20). Also unlike Mad2, Emi1 stabilizes cyclin A in the embryo and requires zinc for its APC inhibitory activity. We find that Emi1 binds the substrate-binding region of Cdc20 and prevents substrate binding to the APC, illustrating a novel mechanism of APC inhibition.
Reimann
J D
JD
Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.
Gardner
B E
BE
Margottin-Goguet
F
F
Jackson
P K
PK
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000502:physiology; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D019925:Cyclin A / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism; D044783:F-Box Proteins; D005656:Fungal Proteins / Q000502:physiology; D006801:Humans; D008025:Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064246:Mad2 Proteins; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins; D010750:Phosphoproteins / Q000502:physiology; D011506:Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D029867:Xenopus Proteins; D014982:Xenopus laevis; D015032:Zinc / Q000494:pharmacology
C577495:CDC20 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A; D019926:Cyclin B; D044783:F-Box Proteins; C429107:FBXO5 protein, Xenopus; C498960:FBXO5 protein, human; D005656:Fungal Proteins; C501382:MAD1 protein, S cerevisiae; C501384:MAD1L1 protein, human; C577695:MAD2 protein, S cerevisiae; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; D011506:Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D029867:Xenopus Proteins; D002237:Carbohydrate Dehydrogenases; C019859:cellobiose-quinone oxidoreductase; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D015032:Zinc