Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) with cyclin A-Cdk2 and cyclin D2-Cdk4 Journal Article
| Authors: | Blain, S. W.; Montalvo, E.; Massagué, J. |
| Article Title: | Differential interaction of the cyclin-dependent kinase (Cdk) inhibitor p27(Kip1) with cyclin A-Cdk2 and cyclin D2-Cdk4 |
| Abstract: | Although p27(Kip1) has been considered a general inhibitor of G1 and S phase cyclin-dependent kinases, we report that the interaction of p27 with two such kinases, cyclin A-Cdk2 and cyclin D-Cdk4, is different. In Mv1Lu cells containing a p27 inducible system, a 6-fold increase over the basal p27 level completely inhibited Cdk2 and cell cycle progression. In contrast, the same or a larger increase in p27 levels did not inhibit Cdk4 or its homologue Cdk6, despite extensive binding to these kinases. A p27-cyclin A-Cdk2 complex formed in vitro was essentially inactive, whereas a p27-cyclin D2-Cdk4 complex was active as a retinoblastoma kinase and served as a substrate for the Cdk-activating kinase Cak. High concentrations of p27 inhibited cyclin D2-Cdk4, apparently by conversion of active complexes into inactive ones by the binding of additional p27 molecules. In contrast to their differential interaction, cyclin A-Cdk2 and cyclin D2-Cdk4 were similarly inhibited by bound p21(Cip1/Waf1). Roles of cyclin A-Cdk2 as a p27 target and cyclin D2- Cdk4 as a p27 reservoir may result from the differential ability of bound p27 to inhibit the kinase subunit in these complexes. |
| Keywords: | proto-oncogene proteins; nonhuman; proteins; animal cell; animals; cell cycle proteins; cell cycle; enzyme inhibition; protein protein interaction; cell line; nerve tissue proteins; animalia; protein kinase inhibitors; enzyme inhibitors; protein-serine-threonine kinases; cyclin-dependent kinase inhibitor p27; tumor suppressor proteins; cycline; cyclin-dependent kinases; cyclins; cyclin a; cyclin dependent kinase inhibitor; enzyme binding; macromolecular substances; cyclin-dependent kinase 4; mink; cyclin-dependent kinase 2; microtubule-associated proteins; enzyme inhibitor complex; cdc2-cdc28 kinases; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 272 |
| Issue: | 41 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1997-10-10 |
| Start Page: | 25863 |
| End Page: | 25872 |
| Language: | English |
| DOI: | 10.1074/jbc.272.41.25863 |
| PUBMED: | 9325318 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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