Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase |
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| Authors: | Koepp D M Schaefer L K Ye X Keyomarsi K Chu C Harper J W Elledge S J |
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| Institution: | Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX, 77030, USA. |
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| Abstract: | Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G1 phase to the S phase of the cell cycle. The amount of cyclin E protein present in the cell is tightly controlled by ubiquitin-mediated proteolysis. Here we identify the ubiquitin ligase responsible for cyclin E ubiquitination as SCFFbw7 and demonstrate that it is functionally conserved in yeast, flies, and mammals. Fbw7 associates specifically with phosphorylated cyclin E, and SCFFbw7 catalyzes cyclin E ubiquitination in vitro. Depletion of Fbw7 leads to accumulation and stabilization of cyclin E in vivo in human and Drosophila melanogaster cells. Multiple F-box proteins contribute to cyclin E stability in yeast, suggesting an overlap in SCF E3 ligase specificity that allows combinatorial control of cyclin E degradation. |
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