Role of the ubiquitin ligase Fbw7 in cancer progression

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• 作者：Yabin Cheng (1)
  Gang Li (1) gangli@mail.ubc.ca
• 关键词：SCF – ; Fbw7 – ; Cancer progression
• 刊名：Cancer and Metastasis Reviews
• 出版年：2012
• 出版时间：June 2012
• 年：2012
• 卷：31
• 期：1-2
• 页码：75-87
• 全文大小：479.1 KB
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• 作者单位：1. Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, 2660 Oak Street, Vancouver, B C V6H 3Z6, Canada
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  
• 出版者：Springer Netherlands
• ISSN：1573-7233

文摘

Fbw7 is a member of F-box family proteins, which constitute one subunit of Skp1, Cul1, and F-box protein (SCF) ubiquitin ligase complex. SCFFbw7 targets a set of well-known oncoproteins, including c-Myc, cyclin E, Notch, c-Jun, and Mcl-1, for ubiquitylation and degradation. Fbw7 provides specificity of the ubiquitylation of these substrate proteins via recognition of a consensus phosphorylated degron. Through regulation of several important proteins, Fbw7 controls diverse cellular processes, including cell-cycle progression, cell proliferation, differentiation, DNA damage response, maintenance of genomic stability, and neural cell stemness. As reduced Fbw7 expression level and loss-of-function mutations are found in a wide range of human cancers, Fbw7 is generally considered as a tumor suppressor. However, the exact mechanisms underlying Fbw7-induced tumor suppression is unclear. This review focuses on regulation network, biological functions, and genetic alteration of Fbw7 in connection with its role in cancer development.