Fbxw7 contributes to tumor suppression by targeting multiple proteins for ubiquitin-dependent degradation

Yo Fujii, Masayoshi Yada, Masaaki Nishiyama, Takumi Kamura, Hidehisa Takahashi, Ryosuke Tsunematsu, Etsuo Susaki, Tadashi Nakagawa, Akinobu Matsumoto, Keiichi I. Nakayama

研究成果: ジャーナルへの寄稿記事

51 引用 (Scopus)

抄録

Fbxw7 (also known as Sel-10, hCdc4 or hAgo) is the F-box protein component of a Skp1-Cul1-F-box protein (SCF) ubiquitin ligase. Fbxw7 contributes to the ubiquitin-mediated degradation of cyclin E, c-Myc, Aurora-A, Notch and c-Jun, all of which appear to function as cell-cycle promoters and oncogenic proteins. Loss of Fbxw7 results in elevated expression of its substrates, which may lead to oncogenesis. However, it remains largely unclear which accumulating substrate is most related to cancer development in Fbxw7-mutant cancer cells. In the present study, we examined the abundance of cyclin E, c-Myc and Aurora-A in seven cancer cell lines, which harbor wild-type (three lines) or mutant (four lines) Fbxw7. Although these three substrates accumulated in the Fbxw7-mutant cells, the extent of increase in the expression of these proteins varied in each line. Forced expression of Fbxw7 reduced the levels of cyclin E, c-Myc and Aurora-A in the Fbxw7-mutant cells. In contrast, a decrease in the expression of cyclin E, c-Myc or Aurora-A by RNA interference significantly suppressed the rate of proliferation and anchorage-independent growth of the Fbxw7-mutant cells. These findings thus suggest that the loss of Fbxw7 results in accumulation of cyclin E, c-Myc and Aurora-A, all of which appear to be required for growth promotion of cancer cells. Fbxw7 seems to regulate the levels of multiple targets to suppress cancer development.

元の言語英語
ページ(範囲)729-736
ページ数8
ジャーナルCancer Science
97
発行部数8
DOI
出版物ステータス出版済み - 8 1 2006

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Cyclin E
Protein Transport
Ubiquitin
F-Box Proteins
Neoplasms
Ligases
Growth
RNA Interference
Cell Cycle
Carcinogenesis
Proteins
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Fbxw7 contributes to tumor suppression by targeting multiple proteins for ubiquitin-dependent degradation. / Fujii, Yo; Yada, Masayoshi; Nishiyama, Masaaki; Kamura, Takumi; Takahashi, Hidehisa; Tsunematsu, Ryosuke; Susaki, Etsuo; Nakagawa, Tadashi; Matsumoto, Akinobu; Nakayama, Keiichi I.

:: Cancer Science, 巻 97, 番号 8, 01.08.2006, p. 729-736.

研究成果: ジャーナルへの寄稿記事

Fujii, Y, Yada, M, Nishiyama, M, Kamura, T, Takahashi, H, Tsunematsu, R, Susaki, E, Nakagawa, T, Matsumoto, A & Nakayama, KI 2006, 'Fbxw7 contributes to tumor suppression by targeting multiple proteins for ubiquitin-dependent degradation', Cancer Science, 巻. 97, 番号 8, pp. 729-736. https://doi.org/10.1111/j.1349-7006.2006.00239.x
Fujii, Yo ; Yada, Masayoshi ; Nishiyama, Masaaki ; Kamura, Takumi ; Takahashi, Hidehisa ; Tsunematsu, Ryosuke ; Susaki, Etsuo ; Nakagawa, Tadashi ; Matsumoto, Akinobu ; Nakayama, Keiichi I. / Fbxw7 contributes to tumor suppression by targeting multiple proteins for ubiquitin-dependent degradation. :: Cancer Science. 2006 ; 巻 97, 番号 8. pp. 729-736.
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abstract = "Fbxw7 (also known as Sel-10, hCdc4 or hAgo) is the F-box protein component of a Skp1-Cul1-F-box protein (SCF) ubiquitin ligase. Fbxw7 contributes to the ubiquitin-mediated degradation of cyclin E, c-Myc, Aurora-A, Notch and c-Jun, all of which appear to function as cell-cycle promoters and oncogenic proteins. Loss of Fbxw7 results in elevated expression of its substrates, which may lead to oncogenesis. However, it remains largely unclear which accumulating substrate is most related to cancer development in Fbxw7-mutant cancer cells. In the present study, we examined the abundance of cyclin E, c-Myc and Aurora-A in seven cancer cell lines, which harbor wild-type (three lines) or mutant (four lines) Fbxw7. Although these three substrates accumulated in the Fbxw7-mutant cells, the extent of increase in the expression of these proteins varied in each line. Forced expression of Fbxw7 reduced the levels of cyclin E, c-Myc and Aurora-A in the Fbxw7-mutant cells. In contrast, a decrease in the expression of cyclin E, c-Myc or Aurora-A by RNA interference significantly suppressed the rate of proliferation and anchorage-independent growth of the Fbxw7-mutant cells. These findings thus suggest that the loss of Fbxw7 results in accumulation of cyclin E, c-Myc and Aurora-A, all of which appear to be required for growth promotion of cancer cells. Fbxw7 seems to regulate the levels of multiple targets to suppress cancer development.",
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AU - Yada, Masayoshi

AU - Nishiyama, Masaaki

AU - Kamura, Takumi

AU - Takahashi, Hidehisa

AU - Tsunematsu, Ryosuke

AU - Susaki, Etsuo

AU - Nakagawa, Tadashi

AU - Matsumoto, Akinobu

AU - Nakayama, Keiichi I.

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N2 - Fbxw7 (also known as Sel-10, hCdc4 or hAgo) is the F-box protein component of a Skp1-Cul1-F-box protein (SCF) ubiquitin ligase. Fbxw7 contributes to the ubiquitin-mediated degradation of cyclin E, c-Myc, Aurora-A, Notch and c-Jun, all of which appear to function as cell-cycle promoters and oncogenic proteins. Loss of Fbxw7 results in elevated expression of its substrates, which may lead to oncogenesis. However, it remains largely unclear which accumulating substrate is most related to cancer development in Fbxw7-mutant cancer cells. In the present study, we examined the abundance of cyclin E, c-Myc and Aurora-A in seven cancer cell lines, which harbor wild-type (three lines) or mutant (four lines) Fbxw7. Although these three substrates accumulated in the Fbxw7-mutant cells, the extent of increase in the expression of these proteins varied in each line. Forced expression of Fbxw7 reduced the levels of cyclin E, c-Myc and Aurora-A in the Fbxw7-mutant cells. In contrast, a decrease in the expression of cyclin E, c-Myc or Aurora-A by RNA interference significantly suppressed the rate of proliferation and anchorage-independent growth of the Fbxw7-mutant cells. These findings thus suggest that the loss of Fbxw7 results in accumulation of cyclin E, c-Myc and Aurora-A, all of which appear to be required for growth promotion of cancer cells. Fbxw7 seems to regulate the levels of multiple targets to suppress cancer development.

AB - Fbxw7 (also known as Sel-10, hCdc4 or hAgo) is the F-box protein component of a Skp1-Cul1-F-box protein (SCF) ubiquitin ligase. Fbxw7 contributes to the ubiquitin-mediated degradation of cyclin E, c-Myc, Aurora-A, Notch and c-Jun, all of which appear to function as cell-cycle promoters and oncogenic proteins. Loss of Fbxw7 results in elevated expression of its substrates, which may lead to oncogenesis. However, it remains largely unclear which accumulating substrate is most related to cancer development in Fbxw7-mutant cancer cells. In the present study, we examined the abundance of cyclin E, c-Myc and Aurora-A in seven cancer cell lines, which harbor wild-type (three lines) or mutant (four lines) Fbxw7. Although these three substrates accumulated in the Fbxw7-mutant cells, the extent of increase in the expression of these proteins varied in each line. Forced expression of Fbxw7 reduced the levels of cyclin E, c-Myc and Aurora-A in the Fbxw7-mutant cells. In contrast, a decrease in the expression of cyclin E, c-Myc or Aurora-A by RNA interference significantly suppressed the rate of proliferation and anchorage-independent growth of the Fbxw7-mutant cells. These findings thus suggest that the loss of Fbxw7 results in accumulation of cyclin E, c-Myc and Aurora-A, all of which appear to be required for growth promotion of cancer cells. Fbxw7 seems to regulate the levels of multiple targets to suppress cancer development.

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