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Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation.
Open accessAbstract
Cyclin E is a mammalian G1 cyclin that is both required and rate limiting for entry into S phase. The expression of cyclin E is periodic, peaking at the G1-S transition and then decaying as S phase progresses. To understand the mechanisms underlying cyclin E periodicity, we have investigated the regulation of cyclin E degradation. We find that cyclin E is degraded by the ubiquitin-proteasome system, and that this degradation is regulated by both cdk2 binding and cdk2 catalytic activity. Free cyclin E is readily ubiquitinated and degraded by the proteasome. Binding to cdk2 protects cyclin E from ubiquitination, and this protection is reversed by cdk2 activity in a process that involves phosphorylation of cyclin E itself. The data are most consistent with a model in which cdk2 activity initiates cyclin E degradation by promoting the disassembly of cyclin E-cdk2 complexes, followed by the ubiquitination and degradation of free cyclin E.
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Citations
Cited by
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
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Sherr, C. J., & Roberts, J. M. (1999) · Genes & Development · doi:10.1101/gad.13.12.1501 · Cited by 6,115
Self-citationSherr, C. J. (1996) · Science · doi:10.1126/science.274.5293.1672 · Cited by 5,379
A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma
Richardson, P. G., Barlogie, B., Berenson, J., Singhal, S., Jagannath, S., Irwin, D., Rajkumar, S. V., Srkalovic, G., Alsina, M., Alexanian, R., et al. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa030288 · Cited by 2,632
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Metadata
- Authors
- Clurman, B. E., Sheaff, R. J., Thress, K., Groudine, M., & Roberts, J. M.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1996-08-15
- Volume
- 10
- Issue
- 16
- Pages
- 1979-1990
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2113273914
- Cited by
- 488
- References
- 0
- Type
- posted content
- Language
- en
- Open access
- diamond
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- Clurman, B. E., Sheaff, R. J., Thress, K., Groudine, M., & Roberts, J. M. (1996). Turnover of cyclin E by the ubiquitin-proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes & Development. https://doi.org/10.1101/gad.10.16.1979
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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