Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication

Keiko Nakayama, Hiroyasu Nagahama, Yohji A. Minamishima, Masaki Matsumoto, Ikuo Nakamichi, Kyoko Kitagawa, Michiko Shirane, Ryosuke Tsunematsu, Tadasuke Tsukiyama, Noriko Ishida, Masatoshi Kitagawa, Keiichi Nakayama, Shigetsugu Hatakeyama

研究成果: ジャーナルへの寄稿記事

583 引用 (Scopus)

抄録

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 G2 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.

元の言語英語
ページ(範囲)2069-2081
ページ数13
ジャーナルEMBO Journal
19
発行部数9
出版物ステータス出版済み - 5 2 2000

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Cyclin E
Centrosome
Polyploidy
SKP Cullin F-Box Protein Ligases
Ubiquitin
Ligases
Cells
F-Box Proteins
Degradation
G2 Phase
Ubiquitination
Periodicity
Proteasome Endopeptidase Complex
Chromosomes
Cell Cycle Checkpoints
S Phase
Cell Cycle
Animals
Apoptosis
Substrates

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

これを引用

Nakayama, K., Nagahama, H., Minamishima, Y. A., Matsumoto, M., Nakamichi, I., Kitagawa, K., ... Hatakeyama, S. (2000). Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication. EMBO Journal, 19(9), 2069-2081.

Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication. / Nakayama, Keiko; Nagahama, Hiroyasu; Minamishima, Yohji A.; Matsumoto, Masaki; Nakamichi, Ikuo; Kitagawa, Kyoko; Shirane, Michiko; Tsunematsu, Ryosuke; Tsukiyama, Tadasuke; Ishida, Noriko; Kitagawa, Masatoshi; Nakayama, Keiichi; Hatakeyama, Shigetsugu.

:: EMBO Journal, 巻 19, 番号 9, 02.05.2000, p. 2069-2081.

研究成果: ジャーナルへの寄稿記事

Nakayama, K, Nagahama, H, Minamishima, YA, Matsumoto, M, Nakamichi, I, Kitagawa, K, Shirane, M, Tsunematsu, R, Tsukiyama, T, Ishida, N, Kitagawa, M, Nakayama, K & Hatakeyama, S 2000, 'Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication', EMBO Journal, 巻. 19, 番号 9, pp. 2069-2081.
Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K その他. Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication. EMBO Journal. 2000 5 2;19(9):2069-2081.
Nakayama, Keiko ; Nagahama, Hiroyasu ; Minamishima, Yohji A. ; Matsumoto, Masaki ; Nakamichi, Ikuo ; Kitagawa, Kyoko ; Shirane, Michiko ; Tsunematsu, Ryosuke ; Tsukiyama, Tadasuke ; Ishida, Noriko ; Kitagawa, Masatoshi ; Nakayama, Keiichi ; Hatakeyama, Shigetsugu. / Targeted disruption of Skp2 results in accumulation of cyclin E and p27 (Kip1), polyploidy and centrosome overduplication. :: EMBO Journal. 2000 ; 巻 19, 番号 9. pp. 2069-2081.
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AU - Tsunematsu, Ryosuke

AU - Tsukiyama, Tadasuke

AU - Ishida, Noriko

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