Journal
SCIENCE
Volume 294, Issue 5540, Pages 173-177Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1065203
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- NIA NIH HHS [R01 AG011085] Funding Source: Medline
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Cyclin E binds and activates the cyclin-dependent kinase Cdk2 and catalyzes the transition from the G(1) 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 SCF Fbw7 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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