Design of a Novel Class of Peptide Inhibitors of Cyclin-dependent Kinase/Cyclin Activation - Université de Montpellier Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2005

Design of a Novel Class of Peptide Inhibitors of Cyclin-dependent Kinase/Cyclin Activation

Résumé

Cyclin dependent kinases (CDKs) are key regulators of the cell cycle progression and therefore constitute excellent targets for the design of anticancer agents. Most of the inhibitors identified to date inhibit kinase activity by interfering with the ATP-binding site of CDKs. We recently proposed that the protein/protein interface and conformational changes required in the molecular mechanism of CDK2-cyclin A activation were potential targets for the design of specific inhibitors of cell cycle progression. To this aim, we have designed and characterized a small peptide, termed C4, derived from amino acids 285-306 in the alpha5 helix of cyclin A. We demonstrate that this peptide does not interfere with complex formation but forms stable complexes with CDK2-cyclin A. The C4 peptide significantly inhibits kinase activity of complexes harboring CDK2 in a competitive fashion with respect to substrates but does not behave as an ATP antagonist. Moreover, when coupled with the protein transduction domain of Tat, the C4 peptide blocks the proliferation of tumor cell lines, thereby constituting a potent lead for the development of specific CDK-cyclin inhibitors.
Fichier principal
Vignette du fichier
PIIS0021925819604564.pdf (444.93 Ko) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03117951 , version 1 (19-03-2021)

Licence

Identifiants

Citer

Claire Gondeau, Sabine Gerbal-Chaloin, Paul Bello, Gudrun Aldrian-Herrada, May Morris, et al.. Design of a Novel Class of Peptide Inhibitors of Cyclin-dependent Kinase/Cyclin Activation. Journal of Biological Chemistry, 2005, 280 (14), pp.13793-13800. ⟨10.1074/jbc.M413690200⟩. ⟨hal-03117951⟩
34 Consultations
34 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More