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A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding
Cyclin-dependent kinase 2 (cdk2) is a central regulator of the mammalian cell cycle. Here we describe the properties of a mutant form of cdk2 identified during large-scale sequencing of protein kinases from cancerous tissue. The mutation substituted a leucine for a proline in the PSTAIRE helix, the...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Pub. Co
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111755/ https://www.ncbi.nlm.nih.gov/pubmed/20399812 http://dx.doi.org/10.1016/j.bbamcr.2010.04.004 |
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author | Child, Emma S. Hendrychová, Tereza McCague, Karen Futreal, Andy Otyepka, Michal Mann, David J. |
author_facet | Child, Emma S. Hendrychová, Tereza McCague, Karen Futreal, Andy Otyepka, Michal Mann, David J. |
author_sort | Child, Emma S. |
collection | PubMed |
description | Cyclin-dependent kinase 2 (cdk2) is a central regulator of the mammalian cell cycle. Here we describe the properties of a mutant form of cdk2 identified during large-scale sequencing of protein kinases from cancerous tissue. The mutation substituted a leucine for a proline in the PSTAIRE helix, the central motif in the interaction of the cdk with its regulatory cyclin subunit. We demonstrate that whilst the mutant cdk2 is considerably impaired in stable cyclin association, it is still able to generate an active kinase that can functionally complement defective cdks in vivo. Molecular dynamic simulations and biophysical measurements indicate that the observed biochemical properties likely stem from increased flexibility within the cyclin-binding helix. |
format | Online Article Text |
id | pubmed-3111755 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Elsevier Pub. Co |
record_format | MEDLINE/PubMed |
spelling | pubmed-31117552011-06-10 A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding Child, Emma S. Hendrychová, Tereza McCague, Karen Futreal, Andy Otyepka, Michal Mann, David J. Biochim Biophys Acta Article Cyclin-dependent kinase 2 (cdk2) is a central regulator of the mammalian cell cycle. Here we describe the properties of a mutant form of cdk2 identified during large-scale sequencing of protein kinases from cancerous tissue. The mutation substituted a leucine for a proline in the PSTAIRE helix, the central motif in the interaction of the cdk with its regulatory cyclin subunit. We demonstrate that whilst the mutant cdk2 is considerably impaired in stable cyclin association, it is still able to generate an active kinase that can functionally complement defective cdks in vivo. Molecular dynamic simulations and biophysical measurements indicate that the observed biochemical properties likely stem from increased flexibility within the cyclin-binding helix. Elsevier Pub. Co 2010-07 /pmc/articles/PMC3111755/ /pubmed/20399812 http://dx.doi.org/10.1016/j.bbamcr.2010.04.004 Text en © 2010 Elsevier B.V. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license |
spellingShingle | Article Child, Emma S. Hendrychová, Tereza McCague, Karen Futreal, Andy Otyepka, Michal Mann, David J. A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
title | A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
title_full | A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
title_fullStr | A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
title_full_unstemmed | A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
title_short | A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
title_sort | cancer-derived mutation in the pstaire helix of cyclin-dependent kinase 2 alters the stability of cyclin binding |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111755/ https://www.ncbi.nlm.nih.gov/pubmed/20399812 http://dx.doi.org/10.1016/j.bbamcr.2010.04.004 |
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