The cyclin box and C-terminus of cyclins A and E specify CDK activation and substrate specificity.
The cyclins and their catalytic partners, the Cyclin Dependent Kinases (CDKs), are essential for progression through the cell cycle. Cyclin/kinase complexes containing cyclins A or E are active primarily in late G1 to S phase and both have been shown to phosphorylate histone H1 and the retinoblastoma gene product (pRb) in vitro. Despite these similarities, cyclins A and E display differences in CDK activation and substrate specificity. We find that in vitro, cyclin E/CDK2 and cyclin A/CDK2 phosphorylate histone H1 similarly but only cyclin A/CDK2 phosphorylates lamin B. While both cyclin A and cyclin E bind CDK1 efficiently, only cyclin A activates CDK1 kinase activity. Using chimeric proteins between cyclins A and E we find that both the cyclin box and C-terminus of cyclins A and E are required for CDK binding, activation and targeting of substrate specificity.
Horton
L E
LE
Institute of Pathology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Templeton
D J
DJ
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D016213:Cyclins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D013379:Substrate Specificity; D014162:Transfection
D016213:Cyclins; D006657:Histones; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D016160:Retinoblastoma Protein; D018844:Cyclin-Dependent Kinases