title: Redundant ubiquitin ligase activities regulate wee1 degradation and mitotic entry.
abstract: 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.
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, Florida 33458, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Smith
authors.forename: Scott
authors.initials: S
authors.lastname: Simanski
authors.forename: Mohammad
authors.initials: M
authors.lastname: Fallahi
authors.forename: Nagi G
authors.initials: NG
authors.lastname: Ayad
mesh_terms: D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D043743:Ubiquitin-Protein Ligase Complexes; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human