Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC.
Entry into mitosis requires the activation of cdk1/cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded. Cyclin B proteolysis is mediated by the anaphase promoting complex, or APC, an E3 ligase that is active at anaphase in mitosis through G1. We ... have identified a G1 substrate of the APC that we have termed Tome-1, for trigger of mitotic entry. Tome-1 is a cytosolic protein required for proper activation of cdk1/cyclin B and mitotic entry. Tome-1 associates with Skp-1 and is required for degradation of the cdk1 inhibitory tyrosine kinase wee1; Tome-1 therefore appears to be acting as part of an SCF-type E3 for wee1. Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cdk1/cyclin B activity and thus mitotic entry and exit.
Mesh Terms:
3T3 Cells, Animals, CDC2 Protein Kinase, Cell Cycle Proteins, Cyclin B, Cytosol, DNA, Complementary, Eukaryotic Cells, G1 Phase, Hela Cells, Humans, Ligases, Mice, Mitosis, Molecular Sequence Data, Nuclear Proteins, Phosphorylation, Protein-Tyrosine Kinases, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Xenopus Proteins
3T3 Cells, Animals, CDC2 Protein Kinase, Cell Cycle Proteins, Cyclin B, Cytosol, DNA, Complementary, Eukaryotic Cells, G1 Phase, Hela Cells, Humans, Ligases, Mice, Mitosis, Molecular Sequence Data, Nuclear Proteins, Phosphorylation, Protein-Tyrosine Kinases, S-Phase Kinase-Associated Proteins, Sequence Homology, Amino Acid, Sequence Homology, Nucleic Acid, Ubiquitin, Ubiquitin-Protein Ligase Complexes, Xenopus Proteins
Cell
Date: Apr. 04, 2003
PubMed ID: 12679038
View in: Pubmed Google Scholar
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