The EMBO journal, 2000-05, Vol.19 (9), p.2069-2081
2000
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- Autor(en) / Beteiligte
- Titel
- Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication
- Ist Teil von
- The EMBO journal, 2000-05, Vol.19 (9), p.2069-2081
- Ort / Verlag
- England
- Erscheinungsjahr
- 2000
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- The ubiquitin-proteasome pathway plays an important role in control of the abundance of cell cycle regulators. Mice lacking Skp2, an F-box protein and substrate recognition component of an Skp1-Cullin-F-box protein (SCF) ubiquitin ligase, were generated. Although Skp2(-/-) animals are viable, cells in the mutant mice contain markedly enlarged nuclei with polyploidy and multiple centrosomes, and show a reduced growth rate and increased apoptosis. Skp2(-/-) cells also exhibit increased accumulation of both cyclin E and p27(Kip1). The elimination of cyclin E during S and G(2) phases is impaired in Skp2(-/-) cells, resulting in loss of cyclin E periodicity. Biochemical studies showed that Skp2 interacts specifically with cyclin E and thereby promotes its ubiquitylation and degradation both in vivo and in vitro. These results suggest that specific degradation of cyclin E and p27(Kip1) is mediated by the SCF(Skp2) ubiquitin ligase complex, and that Skp2 may control chromosome replication and centrosome duplication by determining the abundance of cell cycle regulators.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0261-4189DOI: 10.1093/emboj/19.9.2069Titel-ID: cdi_proquest_miscellaneous_71116947
- Format
- –
- Schlagworte
- Animals, Apoptosis, CDC2-CDC28 Kinases, Cell Cycle Proteins - antagonists & inhibitors, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell Division, Cell Nucleus - genetics, Cell Nucleus - metabolism, Cell Size, Cells, Cultured, Centrosome - metabolism, Cullin Proteins, Cyclin E - antagonists & inhibitors, Cyclin E - metabolism, Cyclin-Dependent Kinase 2, Cyclin-Dependent Kinase Inhibitor p27, Cyclin-Dependent Kinases - metabolism, Fibroblasts - cytology, Gene Deletion, Helminth Proteins - metabolism, Kinetics, Mice, Mice, Knockout, Microtubule-Associated Proteins - metabolism, Molecular Sequence Data, Peptide Synthases - chemistry, Peptide Synthases - genetics, Peptide Synthases - metabolism, Periodicity, Polyploidy, Protein Binding, Protein-Serine-Threonine Kinases - metabolism, S-Phase Kinase-Associated Proteins, SKP Cullin F-Box Protein Ligases, T-Lymphocytes - cytology, Tumor Suppressor Proteins, Ubiquitins - metabolism