Phosphorylation-Dependent Ubiquitination of Cyclin E by the SCF Fbw7 Ubiquitin Ligase
Top Cited Papers
- 5 October 2001
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 294 (5540) , 173-177
- https://doi.org/10.1126/science.1065203
Abstract
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 SCF Fbw7 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.Keywords
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