Phosphorylation-dependent ubiquitination of cyctin E by the SCFFbw7 ubiquitin ligase

D. M. Koepp, L. K. Schaefer, X. Ye, K. Keyomarsi, C. Chu, J. W. Harper, S. J. Elledge

Research output: Contribution to journalArticlepeer-review

606 Scopus citations

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 languageEnglish (US)
Pages (from-to)173-177
Number of pages5
JournalScience
Volume294
Issue number5540
DOIs
StatePublished - Oct 5 2001
Externally publishedYes

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