A cancer-derived mutation in the PSTAIRE helix of cyclin-dependent kinase 2 alters the stability of cyclin binding.
Biochim Biophys Acta
; 1803(7): 858-64, 2010 Jul.
Article
em En
| MEDLINE
| ID: mdl-20399812
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Oncogênicas
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Ciclina E
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Quinase 2 Dependente de Ciclina
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Mutação
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Neoplasias
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2010
Tipo de documento:
Article