beta3-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 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.
Ohtoshi
A
A
Department of Viral Oncology, Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, 170-8455, Japan.
Maeda
T
T
Higashi
H
H
Ashizawa
S
S
Yamada
M
M
Hatakeyama
M
M
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D019925:Cyclin A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli; D007700:Kinetics; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D017384:Sequence Deletion; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
D019925:Cyclin A; C403295:ITGB3BP protein, human; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D011494:Protein Kinases; C102333:histone H1 kinase; D001616:beta-Galactosidase