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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
beta3-endonexin as a novel inhibitor of cyclin A-associated kinase
A Ohtoshi1, T Maeda, H Higashi
1Department of Viral Oncology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 170-8455, Japan.
Abstract:
Cyclin A is indispensable for S phase cell cycle progression and is suggested to be a crucial target of cell adhesion signals. In this study, we demonstrate that beta3-endonexin, a molecule known to associate with the integrin beta3 cytoplasmic domain, specifically binds cyclin A. Deletion of the amino-terminal 52-amino-acid residues including the cyclin-binding RxL motif abolishes the ability of beta3-endonexin to interact with cyclin A. In an in vitro kinase assay, beta3-endonexin inhibits pRB kinase activity associated with cyclin A-Cdk2 while leaving its histone H1 kinase activity unaffected. Coexpression of beta3-endonexin in yeast cells overcomes growth suppression caused by an activation of cyclin A-associated kinase. Our results indicate that beta3-endonexin is a novel cyclin A-binding molecule that regulates cyclin A-associated pRB kinase activity.
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