Activation Domain-dependent Degradation of Somatic Wee1 Kinase |
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| Authors: | Laura Owens Scott Simanski Christopher Squire Anthony Smith Jeff Cartzendafner Valerie Cavett Jennifer Caldwell Busby Trey Sato and Nagi G Ayad |
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| Institution: | From the Departments of ‡Cancer Biology, ;¶Molecular Therapeutics, and ;‖Biochemistry, The Scripps Research Institute, Scripps Florida, Jupiter, Florida 33458 and ;the §School of Biological Sciences and Centre for Molecular Biodiscovery, University of Auckland, Auckland 1001, New Zealand |
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| Abstract: | Cell cycle progression is dependent upon coordinate regulation of kinase and proteolytic pathways. Inhibitors of cell cycle transitions are degraded to allow progression into the subsequent cell cycle phase. For example, the tyrosine kinase and Cdk1 inhibitor Wee1 is degraded during G2 and mitosis to allow mitotic progression. Previous studies suggested that the N terminus of Wee1 directs Wee1 destruction. Using a chemical mutagenesis strategy, we report that multiple regions of Wee1 control its destruction. Most notably, we find that the activation domain of the Wee1 kinase is also required for its degradation. Mutations in this domain inhibit Wee1 degradation in somatic cell extracts and in cells without affecting the overall Wee1 structure or kinase activity. More broadly, these findings suggest that kinase activation domains may be previously unappreciated sites of recognition by the ubiquitin proteasome pathway. |
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| Keywords: | Cdk (cyclin-dependent kinase) Cell Cycle Mitosis Protein Turnover Ubiquitin |
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