Affordable Access

deepdyve-link
Publisher Website

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

Authors
  • Salamina, Marco1
  • Montefiore, Bailey C1
  • Liu, Mengxi2
  • Wood, Daniel J1
  • Heath, Richard1
  • Ault, James R3
  • Wang, Lan-Zhen1
  • Korolchuk, Svitlana1
  • Baslé, Arnaud4
  • Pastok, Martyna W1
  • Reeks, Judith1
  • Tatum, Natalie J1
  • Sobott, Frank3
  • Arold, Stefan T5
  • Pagano, Michele2
  • Noble, Martin E M1
  • Endicott, Jane A6
  • 1 Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • 2 Department of Biochemistry and Molecular Pharmacology, Perlmutter NYU Cancer Center, New York University Grossman School of Medicine, and Howard Hughes Medical Institute, The Alexandria Center of Life Science, East Tower, 450 E, 29th Street, New York, NY 10016, USA.
  • 3 Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.
  • 4 Biosciences Institute, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
  • 5 Division of Biological and Environmental Sciences and Engineering (BESE), Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal 23955-6900, Saudi Arabia; Centre de Biochimie Structurale, CNRS, INSERM, Université de Montpellier, 34090 Montpellier, France. , (France)
  • 6 Newcastle University Centre for Cancer, Translational and Clinical Research Institute, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. Electronic address: [email protected]
Type
Published Article
Journal
Journal of Molecular Biology
Publisher
Elsevier
Publication Date
Jan 07, 2021
Volume
433
Issue
5
Pages
166795–166795
Identifiers
DOI: 10.1016/j.jmb.2020.166795
PMID: 33422522
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Report this publication

Statistics

Seen <100 times