CLONING AND CHARACTERIZATION OF THE XENOPUS CYCLIN-DEPENDENT KINASE INHIBITOR P27(XIC1)

We have isolated a gene encoding Xic-1, a 27-kDa cyclin-dependent kina se (Cdk) inhibitor from Xenopus ovary that shares significant homology with both mammalian CIP1 and Kip1/Rip2. The N- and C-terminal halves of Xic-1 are sufficient for interacting with Cdks and proliferating ce ll nuclear antigen, respectively. Recombinant Xic-1 inhibits Xenopus c yclin E/Cdk2, cyclin A/Cdk2, and cyclin B/Cdc2 activities, although wi th quite different IC50 values. Truncation of the N terminus of Xic-1 increases the IC50 value for cyclin A/Cdk2 50-fold with no effect on t he inhibition of cyclin E/Cdk2 or cyclin B/Cdc2. Xic-1 inhibits both s ingle-stranded and nuclear DNA synthesis in egg extracts, an effect re versed by proliferating cell nuclear antigen or cyclin E/Cdk2, respect ively. These results suggest a function for Xic-1 in the control of DN A synthesis by cyclin E/Cdk2.