Published In

Journal of Cell Science

Document Type

Article

Publication Date

11-2019

Subjects

Ubiquitin, Protein binding, Cyclin-dependent kinases, Proteins -- Metabolism, Cancer

Abstract

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 ubiquitylates phosphorylated cyclin E, but the mechanism through which Cul3 ubiquitylates cyclin E is poorly understood. In experiments to ascertain how Cul3 mediates cyclin E destruction, we identified a degron on cyclin E that Cul3 targets for ubiquitylation. 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-mediated degradation pathway. This mechanism helps to explain the increased activity that is associated with the truncated cyclin E variants that occurs in some cancers.

Description

Originally appeared in the Journal of Cell Science, vol. 132, no. 21, 2019. Published by the Company of Biologists. May be accessed at https://doi.org/10.1242/jcs.233049

DOI

10.1242/jcs.233049

Persistent Identifier

https://archives.pdx.edu/ds/psu/30435

Available for download on Saturday, November 21, 2020

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