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.
Ayad
Nagi G
NG
Department of Cell Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Rankin
Susannah
S
Murakami
Monica
M
Jebanathirajah
Judith
J
Gygi
Steven
S
Kirschner
Marc W
MW
D016475:3T3 Cells; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D016193:G1 Phase / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008938:Mitosis / Q000235:genetics*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D025801:Ubiquitin / Q000235:genetics / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes; D029867:Xenopus Proteins / Q000235:genetics / Q000302:isolation & purification*
C473797:CDCA3 protein, Xenopus; C473796:CDCA3 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D018076:DNA, Complementary; D009687:Nuclear Proteins; D044786:S-Phase Kinase-Associated Proteins; C473795:Tome-1 protein, mouse; D025801:Ubiquitin; D029867:Xenopus Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human; C499348:Wee1 protein, mouse; D016203:CDC2 Protein Kinase; D008025:Ligases