Cyclin E and its binding partner Cdk2 control the G1/S transition in mammalian cells. Increased levels of cyclin E are found in some cancers. Additionally, proteolytic removal of the cyclin E N-terminus occurs in some cancers and is associated with increased cyclin E/Cdk2 activity and poor clinical prognosis. Cyclin E levels are tightly regulated and controlled in part through ubiquitin-mediated degradation initiated by one of two E3 ligases, Cul1 and Cul3. Cul1 ubiquitinates phosphorylated cyclin E, but the mechanism Cul3 uses to ubiquitinate cyclin E is poorly understood. To ascertain how Cul3 mediates cyclin E destruction, we identified a degron on cyclin E that Cul3 targets for ubiquitination. Recognition of the degron and binding of Cul3 does not require a BTB domain-containing adaptor protein. Additionally, this degron is lacking in N-terminally truncated cyclin E. Our results describe a mechanism whereby N-terminally truncated cyclin E can avoid the Cul3 degradation pathway. This mechanism helps to explain the increased activity that is associated with the truncated cyclin E variants that occur in some cancers.
Cul3 regulates cyclin E1 protein abundance via a degron located within the N-terminal region of cyclin E
Currently Viewing Accepted Manuscript - Newer Version Available
Brittney Davidge, Katia Graziella de Oliveira Rebola, Larry N. Agbor, Curt D. Sigmund, Jeffrey D. Singer; Cul3 regulates cyclin E1 protein abundance via a degron located within the N-terminal region of cyclin E. J Cell Sci 2019; jcs.233049. doi: https://doi.org/10.1242/jcs.233049
Download citation file:
Advertisement
Imaging Cell Architecture and Dynamics
We are still welcoming submissions for our upcoming Special Issue: Imaging Cell Architecture and Dynamics. This issue will be coordinated by two Guest Editors: Lucy Collinson (The Francis Crick Institute, UK) and Guillaume Jacquemet (University of Turku, Finland). Extended submission deadline: 29 March 2024.
Journal of Cell Science - more than just a journal
People who know JCS well will know that we're more than just a journal and that our community – the cell biology community – really is at the heart of everything we do. Read the full Editorial by Editor-in-Chief Michael Way and Executive Editor Seema Grewal.
2024 Journal Meeting 'Diversity and Evolution in Cell Biology'
Registration is open for our 2024 Journal Meeting Diversity and Evolution in Cell Biology, which aims to bring together evolutionary biologists and cell biologists investigating diverse aspects of cellular physiology. Submit your abstract by 5 April. Final registration deadline: 3 May 2024.
Workshop: Roles of Lipids in Nuclear Homeostasis and Genome Stability
Early-career researchers interested in the roles of nuclear lipids, apply now for one of the ten funded places at this Workshop, which will take place 14-17 October 2024. Application deadline: 19 April.
Reasons to submit to Journal of Cell Science
There are many benefits to publishing in Journal of Cell Science - read more about why you should choose JCS or visit our submission page now.