Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC

Nagi G. Ayad, Susannah Rankin, Monica Murakami, Judith Jebanathirajah, Steven Gygi, Marc W. Kirschner

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)101-113
Number of pages13
JournalCell
Volume113
Issue number1
DOIs
StatePublished - Apr 4 2003
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Ayad, N. G., Rankin, S., Murakami, M., Jebanathirajah, J., Gygi, S., & Kirschner, M. W. (2003). Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC. Cell, 113(1), 101-113. https://doi.org/10.1016/S0092-8674(03)00232-0