Molecular Info® Copy Right © 2001
Institute of Molecular Development LLC
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Phosphorylation-Dependent Ubiquitination of Cyclin E by the SCFFbw7 Ubiquitin Ligase
Deanna M. Koepp, Laura K. Schaefer, Xin Ye, Khandan Keyomarsi, Claire Chu, J. Wade Harper, Stephen J. Elledge
The Science, October 2001, 294 (5540): 173-177.
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.
SCFFbw7, the ubiquitin ligase responsible for cyclin E ubiquitination, 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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