Regulation of cell proliferation and tumorigenesis by ubiquitin-proteasome pathway

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The strict regulation of protein degradation by the ubiquitin-proteasome pathway is pivotal for cell cycle progression. Skp2 and Fbw7 are F-box proteins that are substrate-recognition subunits of the SCF-type ubiquitin ligase complex and involved in cell cycle entry and exit. Skp2 promotes the degradation of negative regulators of the cell cycle, such as p27, and facilitates the cell cycle entry. On the other hand, Fbw7 promotes the degradation of positive regulators of the cell cycle, such as c-Myc, and induces the cell cycle exit. We have demonstrated the in vivo roles of Skp2 and Fbw7 in cell cycle regulation using gene-targeting technology in mice. Consistent with our animal models, clinical studies have suggested Skp2 as an oncogene and Fbw7 as an oncosuppressor gene. These accumulating lines of evidence support the notion that Skp2 and Fbw7 are involved in cell cycle regulation and tumorigenesis.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
Issue number6
Publication statusPublished - Nov 1 2008


All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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