Redundant ubiquitin ligase activities regulate wee1 degradation and mitotic entry.

The irreversible nature of mitotic entry is due to the activation of mitosis specific kinases such as cdk1/cyclin B. Cdk1/cyclin B induces activation of mitosis by promoting phosphatases while suppressing inhibitory factors such as the tyrosine kinase wee1. Since wee1 keeps cdk1/cyclin B inactive during the S and G2 phases, its activity must be down-regulated for mitotic progression to occur. One mechanism of suppressing wee1 activity is ubiquitin-dependent proteolysis. Cdk1/cyclin B1 phosphorylates wee1, targeting it for recognition by ubiquitin ligases and subsequent proteasomal degradation. One of the ubiquitin ligases promoting wee1 destruction during mitosis is the SCF(beta-trcp) complex. We demonstrate that this complex, and a second SCF complex containing the F-box protein Tome-1, regulate wee1 degradation during the S and G2 phases of the cell cycle. Therefore, redundant ubiquitin ligase activities promote efficient mitotic entry of eukaryotic cells.