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Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor.
- Source :
-
Genes & development [Genes Dev] 2006 Sep 01; Vol. 20 (17), pp. 2410-20. Date of Electronic Publication: 2006 Aug 18. - Publication Year :
- 2006
-
Abstract
- The periodic destruction of mitotic cyclins is triggered by the activation of the anaphase-promoting complex/cyclosome (APC/C) in mitosis. Although the ability of the APC/C to recognize destruction box (D-box) substrates oscillates throughout the cell cycle, the mechanism regulating APC/C binding to D-box substrates remains unclear. Here, we show that the APC/C inhibitor Emi1 tightly binds both the APC/C and its Cdh1 activator, binds to the D-box receptor site on the APC/C(Cdh1), and competes with APC/C substrates for D-box binding. Emi1 itself contains a conserved C-terminal D-box, which provides APC/C-binding affinity, and a conserved zinc-binding region (ZBR), which antagonizes APC/C E3 ligase activity independent of tight APC binding. Mutation of the ZBR converts Emi1 into a D-box-dependent APC/C substrate. The identification of a direct Emi1-APC/C complex further explains how Emi1 functions as a stabilizing factor for cyclin accumulation and the need to destroy Emi1 for APC/C activation in mitosis. The combination of a degron/E3 recognition site and an anti-ligase function in Emi1 suggests a general model for how E3 substrates evolve to become pseudosubstrate inhibitors.
- Subjects :
- Amino Acid Motifs
Anaphase-Promoting Complex-Cyclosome
Antigens, CD
Binding, Competitive
Cadherins metabolism
Cadherins physiology
Cell Cycle Proteins metabolism
Cell Nucleus enzymology
Cell Nucleus metabolism
Conserved Sequence
F-Box Proteins metabolism
HeLa Cells
Humans
Interphase physiology
Protein Binding
Substrate Specificity
Cell Cycle Proteins physiology
Enzyme Inhibitors metabolism
F-Box Proteins physiology
Ubiquitin-Protein Ligase Complexes antagonists & inhibitors
Ubiquitin-Protein Ligase Complexes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0890-9369
- Volume :
- 20
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Genes & development
- Publication Type :
- Academic Journal
- Accession number :
- 16921029
- Full Text :
- https://doi.org/10.1101/gad.1454006