β3-endonexin as a novel inhibitor of cyclin A-associated kinase

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 beta 3-endonexin, a molecule known to associate with the integrin beta 3 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 beta 3-endonexin to interact with cyclin A. In an in vitro kinase assay, beta 3-endonexin inhibits pRB kinase activity associated with cyclin A-Cdk2 while leaving its histone H1 kinase activity unaffected. Coexpression of beta 3-endonexin in yeast cells overcomes growth suppression caused by an activation of cyclin A-associated kinase. Our results indicate that beta 3-endonexin is a novel cyclin A-binding molecule that regulates cyclin A-associated pRB kinase activity. (C) 2000 Academic Press.