Abstract
We have discovered an early mitotic inhibitor, Emi1, which regulates mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Emi1 is a conserved F box protein containing a zinc binding region essential for APC inhibition. Emi1 accumulates before mitosis and is ubiquitylated and destroyed in mitosis, independent of the APC. Emi1 immunodepletion from cycling Xenopus extracts strongly delays cyclin B accumulation and mitotic entry, whereas nondestructible Emi1 stabilizes APC substrates and causes a mitotic block. Emi1 binds the APC activator Cdc20, and Cdc20 can rescue an Emi1-induced block to cyclin B destruction. Our results suggest that Emi1 regulates progression through early mitosis by preventing premature APC activation, and may help explain the well-known delay between cyclin B/Cdc2 activation and cyclin B destruction.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine Triphosphatases / genetics
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Amino Acid Sequence
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Anaphase-Promoting Complex-Cyclosome
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Animals
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Cdc20 Proteins
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Cell Cycle Proteins / genetics*
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Cell Cycle Proteins / metabolism*
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Conserved Sequence
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Cyclin A / metabolism
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Cyclin B / metabolism
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Drosophila
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Drosophila Proteins*
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In Vitro Techniques
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Ligases / metabolism*
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Membrane Proteins / genetics
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Mice
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Mitosis / physiology*
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Molecular Sequence Data
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Oocytes / cytology
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Oocytes / physiology
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Proteins / metabolism*
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Rabbits
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Ubiquitin-Protein Ligase Complexes*
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Ubiquitin-Protein Ligases
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Xenopus
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Xenopus Proteins
Substances
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Cdc20 Proteins
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Cdc20 protein, mouse
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Cell Cycle Proteins
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CycB protein, Drosophila
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Cyclin A
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Cyclin B
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Drosophila Proteins
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FBXO5 protein, Xenopus
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Fbxo5 protein, mouse
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Membrane Proteins
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Proteins
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Rca1 protein, Drosophila
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Xenopus Proteins
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Ubiquitin-Protein Ligases
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Adenosine Triphosphatases
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Ligases