Prophase destruction of Emi1 by the SCF(betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase

Progression through mitosis occurs because cyclin B/Cdc2 activation induces the anaphase promoting complex (APC) to cause cyclin B destruction and mitotic exit. To ensure that cyclin B/Cdc2 does not prematurely activate the APC in early mitosis, there must be a mechanism delaying APC activation. Emi...

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Bibliographic Details
Published in:Developmental cell 2003-06, Vol.4 (6), p.813-826
Main Authors: Margottin-Goguet, Florence, Hsu, Jerry Y, Loktev, Alexander, Hsieh, Harn Mei, Reimann, Julie D R, Jackson, Peter K
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Amino Acid Sequence
Animals
beta-Transducin Repeat-Containing Proteins
Binding Sites
CDC2 Protein Kinase - genetics
CDC2 Protein Kinase - metabolism
Cell Cycle - drug effects
Cell Cycle Proteins - metabolism
Cell Line
Consensus Sequence
Cyclin A - metabolism
Cyclin B - metabolism
Drosophila Proteins
Enzyme Activation
F-Box Proteins
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Humans
Mitosis - drug effects
Models, Biological
Mutation
Nocodazole - pharmacology
Oocytes - cytology
Oocytes - physiology
Peptide Synthases - metabolism
Phosphorylation
SKP Cullin F-Box Protein Ligases
Swine
Time Factors
Xenopus
Xenopus Proteins
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Summary:Progression through mitosis occurs because cyclin B/Cdc2 activation induces the anaphase promoting complex (APC) to cause cyclin B destruction and mitotic exit. To ensure that cyclin B/Cdc2 does not prematurely activate the APC in early mitosis, there must be a mechanism delaying APC activation. Emi1 is a protein capable of inhibiting the APC in S and G2. We show here that Emi1 is phosphorylated by Cdc2, and on a DSGxxS consensus site, is subsequently recognized by the SCF(betaTrCP/Slimb) ubiquitin ligase and destroyed, thus providing a delay for APC activation. Failure of betaTrCP-dependent Emi1 destruction stabilizes APC substrates and results in mitotic catastrophe including centrosome overduplication, potentially explaining mitotic deficiencies in Drosophila Slimb/betaTrCP mutants. We hypothesize that Emi1 destruction relieves a late prophase checkpoint for APC activation.
ISSN:1534-5807
DOI:10.1016/S1534-5807(03)00153-9