Cloning and characterization of the Xenopus cyclin-dependent kinase inhibitor p27XIC1.
We have isolated a gene encoding Xic-1, a 27-kDa cyclin-dependent kinase (Cdk) inhibitor from Xenopus ovary that shares significant homology with both mammalian CIP1 and Kip1/Kip2. The N- and C-terminal halves of Xic-1 are sufficient for interacting with Cdks and proliferating cell nuclear antigen, respectively. Recombinant Xic-1 inhibits Xenopus cyclin E/Cdk2, cyclin A/Cdk2 and cyclin B/Cdc2 activities, although with 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 the inhibition of cyclin E/Cdk2 or cyclin B/Cdc2.Xic-1 inhibits both single-stranded and nuclear DNA synthesis in egg extracts, an effect reversed by proliferating cell nuclear antigen or cyclin E/Cdk2, respectively. These results suggest a function for Xic-1 in the control of DNA synthesis by cyclin E/Cdk2.
D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D016213:Cyclins / Q000502:physiology*; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008969:Molecular Sequence Data; D010053:Ovary / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D025521:Tumor Suppressor Proteins; D014981:Xenopus; D029867:Xenopus Proteins
D018797:Cell Cycle Proteins; D016213:Cyclins; D017931:DNA Primers; D004791:Enzyme Inhibitors; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D029867:Xenopus Proteins; C493963:Xicl protein, Xenopus; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases