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Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation

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.

Publication metadata

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


DOI: 10.1016/j.jmb.2020.166795

PubMed id: 33422522


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Funder referenceFunder name
C2115/A21421Cancer Research UK CRUK (closed comp)
MR/N009738/1Medical Research Council (MRC)