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.
Original language | English (US) |
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Pages (from-to) | 173-177 |
Number of pages | 5 |
Journal | Science |
Volume | 294 |
Issue number | 5540 |
DOIs | |
State | Published - Oct 5 2001 |
Externally published | Yes |