Targeted disruption of Skp2 results in accumulation of cyclin E and p27Kip1, polyploidy and centrosome overduplication

Autor: Noriko Ishida, Keiko Nakayama, Yohji A. Minamishima, Masaki Matsumoto, Hiroyasu Nagahama, Michiko Shirane, Masatoshi Kitagawa, Keiichi I. Nakayama, Ikuo Nakamichi, Tadasuke Tsukiyama, Shigetsugu Hatakeyama, Ryosuke Tsunematsu, Kyoko Kitagawa
Rok vydání: 2000
Předmět:
Periodicity
Cyclin E
T-Lymphocytes
Molecular Sequence Data
Apoptosis
Cell Cycle Proteins
Protein Serine-Threonine Kinases
General Biochemistry
Genetics and Molecular Biology
Polyploidy
Mice
SCF complex
Cyclin-dependent kinase
CDC2-CDC28 Kinases
Animals
Centrosome duplication
Cell division control protein 4
Peptide Synthases
S-Phase Kinase-Associated Proteins
Ubiquitins
Molecular Biology
Cells
Cultured
Cell Size
Cell Nucleus
Centrosome
Mice
Knockout
SKP Cullin F-Box Protein Ligases
General Immunology and Microbiology
biology
Tumor Suppressor Proteins
General Neuroscience
Cyclin-Dependent Kinase 2
Helminth Proteins
Articles
Fibroblasts
Cell cycle
Cullin Proteins
Molecular biology
Cyclin-Dependent Kinases
Ubiquitin ligase
Cell biology
Kinetics
Ubiquitin ligase complex
biology.protein
Microtubule-Associated Proteins
Cell Division
Cyclin-Dependent Kinase Inhibitor p27
Gene Deletion
Protein Binding
Zdroj: Scopus-Elsevier
ISSN: 1460-2075
DOI: 10.1093/emboj/19.9.2069
Popis: 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.
Databáze: OpenAIRE
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