| http://purl.uniprot.org/citations/10323868 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10323868 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/10323868 | http://www.w3.org/2000/01/rdf-schema#comment | "The cellular abundance of the cyclin-dependent kinase (Cdk) inhibitor p27 is regulated by the ubiquitin-proteasome system. Activation of p27 degradation is seen in proliferating cells and in many types of aggressive human carcinomas. p27 can be phosphorylated on threonine 187 by Cdks, and cyclin E/Cdk2 overexpression can stimulate the degradation of wild-type p27, but not of a threonine 187-to-alanine p27 mutant [p27(T187A)]. However, whether threonine 187 phosphorylation stimulates p27 degradation through the ubiquitin-proteasome system or an alternative pathway is still not known. Here, we demonstrate that p27 ubiquitination (as assayed in vivo and in an in vitro reconstituted system) is cell-cycle regulated and that Cdk activity is required for the in vitro ubiquitination of p27. Furthermore, ubiquitination of wild-type p27, but not of p27(T187A), can occur in G1-enriched extracts only upon addition of cyclin E/Cdk2 or cyclin A/Cdk2. Using a phosphothreonine 187 site-specific antibody for p27, we show that threonine 187 phosphorylation of p27 is also cell-cycle dependent, being present in proliferating cells but undetectable in G1 cells. Finally, we show that in addition to threonine 187 phosphorylation, efficient p27 ubiquitination requires formation of a trimeric complex with the cyclin and Cdk subunits. In fact, cyclin B/Cdk1 which can phosphorylate p27 efficiently, but cannot form a stable complex with it, is unable to stimulate p27 ubiquitination by G1 extracts. Furthermore, another p27 mutant [p27(CK-)] that can be phosphorylated by cyclin E/Cdk2 but cannot bind this kinase complex, is refractory to ubiquitination. Thus throughout the cell cycle, both phosphorylation and trimeric complex formation act as signals for the ubiquitination of a Cdk inhibitor."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.org/dc/terms/identifier | "doi:10.1101/gad.13.9.1181"xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.org/dc/terms/identifier | "doi:10.1101/gad.13.9.1181"xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Draetta G.F."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Draetta G.F."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Pagano M."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Pagano M."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Hershko A."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Hershko A."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Montagnoli A."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Montagnoli A."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Fiore F."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Fiore F."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Carrano A.C."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Carrano A.C."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Eytan E."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/author | "Eytan E."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/date | "1999"xsd:gYear |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/name | "Genes Dev."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/name | "Genes Dev."xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/pages | "1181-1189"xsd:string |
| http://purl.uniprot.org/citations/10323868 | http://purl.uniprot.org/core/pages | "1181-1189"xsd:string |