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

The SCF(SKP2) 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...

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Autores principales: Salamina, Marco, Montefiore, Bailey C., Liu, Mengxi, Wood, Daniel J., Heath, Richard, Ault, James R., Wang, Lan-Zhen, Korolchuk, Svitlana, Baslé, Arnaud, Pastok, Martyna W., Reeks, Judith, Tatum, Natalie J., Sobott, Frank, Arold, Stefan T., Pagano, Michele, Noble, Martin E.M., Endicott, Jane A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895821/
https://www.ncbi.nlm.nih.gov/pubmed/33422522
http://dx.doi.org/10.1016/j.jmb.2020.166795
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author Salamina, Marco
Montefiore, Bailey C.
Liu, Mengxi
Wood, Daniel J.
Heath, Richard
Ault, James R.
Wang, Lan-Zhen
Korolchuk, Svitlana
Baslé, Arnaud
Pastok, Martyna W.
Reeks, Judith
Tatum, Natalie J.
Sobott, Frank
Arold, Stefan T.
Pagano, Michele
Noble, Martin E.M.
Endicott, Jane A.
author_facet Salamina, Marco
Montefiore, Bailey C.
Liu, Mengxi
Wood, Daniel J.
Heath, Richard
Ault, James R.
Wang, Lan-Zhen
Korolchuk, Svitlana
Baslé, Arnaud
Pastok, Martyna W.
Reeks, Judith
Tatum, Natalie J.
Sobott, Frank
Arold, Stefan T.
Pagano, Michele
Noble, Martin E.M.
Endicott, Jane A.
author_sort Salamina, Marco
collection PubMed
description The SCF(SKP2) 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.
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spelling pubmed-78958212021-03-05 Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation Salamina, Marco Montefiore, Bailey C. Liu, Mengxi Wood, Daniel J. Heath, Richard Ault, James R. Wang, Lan-Zhen Korolchuk, Svitlana Baslé, Arnaud Pastok, Martyna W. Reeks, Judith Tatum, Natalie J. Sobott, Frank Arold, Stefan T. Pagano, Michele Noble, Martin E.M. Endicott, Jane A. J Mol Biol Research Article The SCF(SKP2) 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. Elsevier 2021-03-05 /pmc/articles/PMC7895821/ /pubmed/33422522 http://dx.doi.org/10.1016/j.jmb.2020.166795 Text en © 2021 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Salamina, Marco
Montefiore, Bailey C.
Liu, Mengxi
Wood, Daniel J.
Heath, Richard
Ault, James R.
Wang, Lan-Zhen
Korolchuk, Svitlana
Baslé, Arnaud
Pastok, Martyna W.
Reeks, Judith
Tatum, Natalie J.
Sobott, Frank
Arold, Stefan T.
Pagano, Michele
Noble, Martin E.M.
Endicott, Jane A.
Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation
title Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation
title_full Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation
title_fullStr Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation
title_full_unstemmed Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation
title_short Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation
title_sort discriminative skp2 interactions with cdk-cyclin complexes support a cyclin a-specific role in p27kip1 degradation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895821/
https://www.ncbi.nlm.nih.gov/pubmed/33422522
http://dx.doi.org/10.1016/j.jmb.2020.166795
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