THE CYCLIN BOX AND C-TERMINUS OF CYCLIN-A AND CYCLIN-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 Lat e G(1) to S phase and both have been shown to phosphorylate histone H1 and the retinoblastoma gene product (pRb) in vitro. Despite these sim ilarities, cyclins A and E display differences in CDK activation and s ubstrate specificity. We find that in vitro, cyclin E/CDK2 and cyclin A/CDK2 phosphorylate histone H1 similarly but only cyclin A/CDK2 phosp horylates lamin B. While both cyclin A and cyclin E bind CDK1 efficien tly, only cyclin A activates CDK1 kinase activity. Using chimeric prot eins between cyclins A and E we find that both the cyclin box and C-te rminus of cyclins A and E are required for CDK binding, activation and targeting of substrate specificity.