Identification of a cyclin-cdk2 recognition motif present in substrates and p21-like cyclin-dependent kinase inhibitors
| Autor: | Peter D. Adams, William G. Kaelin, S K Sharma, William R. Sellers, C M Nalin, A D Wu |
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| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Cyclin D Cyclin A Molecular Sequence Data Biology Protein Serine-Threonine Kinases Cell Line Substrate Specificity Cyclin D1 Cyclin-dependent kinase Cyclins CDC2-CDC28 Kinases Animals Humans Amino Acid Sequence Molecular Biology Cyclin-dependent kinase 1 Cyclin binding Binding Sites Cyclin-Dependent Kinase 2 Cell Biology Cyclin-Dependent Kinases Cell biology Biochemistry biology.protein Cyclin-dependent kinase complex biological phenomena cell phenomena and immunity Cyclin A2 Gene Deletion Research Article |
| Popis: | Understanding how cyclin-cdk complexes recognize their substrates is a central problem in cell cycle biology. We identified an E2F1-derived eight-residue peptide which blocked the binding of cyclin A and E-cdk2 complexes to E2F1 and p21. Short peptides spanning similar sequences in p107, p130, and p21-like cdk inhibitors likewise bound to cyclin A-cdk2 and cyclin E-cdk2. In addition, these peptides promoted formation of stable cyclin A-cdk2 complexes in vitro but inhibited the phosphorylation of the retinoblastoma protein by cyclin A- but not cyclin B-associated kinases. Mutation of the cyclin-cdk2 binding motifs in p107 and E2F1 likewise prevented their phosphorylation by cyclin A-associated kinases in vitro. The cdk inhibitor p21 was found to contain two functional copies of this recognition motif, as determined by in vitro kinase binding/inhibition assays and in vivo growth suppression assays. Thus, these studies have identified a cyclin A- and E-cdk2 substrate recognition motif. Furthermore, these data suggest that p21-like cdk inhibitors function, at least in part, by blocking the interaction of substrates with cyclin-cdk2 complexes. |
| Databáze: | OpenAIRE |
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