beta3-endonexin as a novel inhibitor of cyclin A-associated kinase

Biochem Biophys Res Commun. 2000 Jan 27;267(3):947-52. doi: 10.1006/bbrc.1999.2007.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Cycle
  • Cyclin A / chemistry
  • Cyclin A / genetics
  • Cyclin A / metabolism*
  • Escherichia coli
  • Kinetics
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • Protein Kinases / metabolism*
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae
  • Sequence Deletion
  • Transfection
  • beta-Galactosidase / metabolism

Substances

  • Cyclin A
  • ITGB3BP protein, human
  • Nuclear Proteins
  • Protein Kinase Inhibitors
  • Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Protein Kinases
  • histone H1 kinase
  • beta-Galactosidase