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Lookup NU author(s): Dr Marco Salamina, Dr Richard Heath, Svitlana Korolchuk, Dr Arnaud Basle, Dr Martyna PastokORCiD, Dr Judith Reeks, Dr Natalie TatumORCiD, Professor Martin NobleORCiD, Professor Jane Endicott
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021 The Author(s). The SCFSKP2 ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution of stable complexes containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated by the CDK regulatory subunit CKS1. We further show that a direct interaction between a SKP2 N-terminal motif and cyclin A can stabilize SKP1-SKP2-CDK2-cyclin A complexes in the absence of CKS1. We identify the SKP2 binding site on cyclin A and demonstrate the site is not present in cyclin B or cyclin E. This site is distinct from but overlapping with features that mediate binding of p27KIP1 and other G1 cyclin regulators to cyclin A. We propose that the capacity of SKP2 to engage with CDK2-cyclin A by more than one structural mechanism provides a way to fine tune the degradation of p27KIP1 and distinguishes cyclin A from other G1 cyclins to ensure orderly cell cycle progression.
Author(s): Salamina M, Montefiore BC, Liu M, Wood DJ, Heath R, Ault JR, Wang L-Z, Korolchuk S, Basle A, Pastok MW, Reeks J, Tatum NJ, Sobott F, Arold ST, Pagano M, Noble MEM, Endicott JA
Publication type: Article
Publication status: Published
Journal: Journal of Molecular Biology
Year: 2021
Volume: 433
Issue: 5
Print publication date: 05/03/2021
Online publication date: 07/01/2021
Acceptance date: 28/12/2020
Date deposited: 26/07/2021
ISSN (print): 0022-2836
ISSN (electronic): 1089-8638
Publisher: Academic Press
URL: https://doi.org/10.1016/j.jmb.2020.166795
DOI: 10.1016/j.jmb.2020.166795
PubMed id: 33422522
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