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Phosphorylation-Dependent Ubiquitination of Cyclin E by the SCF Fbw7 Ubiquitin Ligase
Open accessAbstract
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.
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Citations
Cited by
Function and regulation of cullin–RING ubiquitin ligases
Petroski, M. D., & Deshaies, R. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1547 · Cited by 2,148
Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex
Zheng, N., Schulman, B. A., Song, L., Miller, J. J., Jeffrey, P. D., Wang, P., Chu, C., Koepp, D. M., Elledge, S. J., Pagano, M., et al. (2002) · Nature · doi:10.1038/416703a · Cited by 1,507
Self-citationThe SCF ubiquitin ligase: insights into a molecular machine
Cardozo, T., & Pagano, M. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1471 · Cited by 1,114
Welcker, M., & Clurman, B. E. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2290 · Cited by 1,084
Auxin Receptors and Plant Development: A New Signaling Paradigm
Mockaitis, K., & Estelle, M. (2008) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.23.090506.123214 · Cited by 651
Metadata
- Authors
- Koepp, D. M., Schaefer, L. K., Ye, X., Keyomarsi, K., Chu, C., Harper, J. W., & Elledge, S. J.
- Venue
- Science
- Published
- 2001-10-05
- Volume
- 294
- Issue
- 5540
- Pages
- 173-177
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2126344344
- Cited by
- 762
- References
- 0
- FWCI
- 13.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Koepp, D. M., Schaefer, L. K., Ye, X., Keyomarsi, K., Chu, C., Harper, J. W., & Elledge, S. J. (2001). Phosphorylation-Dependent Ubiquitination of Cyclin E by the SCF Fbw7 Ubiquitin Ligase. Science. https://doi.org/10.1126/science.1065203
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