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Volume 40 Issue 3
Mar.  2013
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Article Navigation >  Journal of Genetics and Genomics  > 2013  >  40(3): 97-106

Role of SKP1-CUL1-F-Box-Protein (SCF) E3 Ubiquitin Ligases in Skin Cancer

doi: 10.1016/j.jgg.2013.02.001
  • a 

    Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, MI 48109, USA

  • b 

    School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China

  • c 

    Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA

More Information
  • Corresponding author: E-mail address: sunyi@umich.edu (Yi Sun)
  • Received Date: 2013-01-17
  • Accepted Date: 2013-02-04
  • Rev Recd Date: 2013-01-30
    • Available Online: 2013-02-09
  • Publish Date: 2013-03-20
    Abstract
  • Many biological processes such as cell proliferation, differentiation, and cell death depend precisely on the timely synthesis and degradation of key regulatory proteins. While protein synthesis can be regulated at multiple levels, protein degradation is mainly controlled by the ubiquitin–proteasome system (UPS), which consists of two distinct steps: (1) ubiquitylation of targeted protein by E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase, and (2) subsequent degradation by the 26S proteasome. Among all E3 ubiquitin ligases, the SCF (SKP1-CUL1-F-box protein) E3 ligases are the largest family and are responsible for the turnover of many key regulatory proteins. Aberrant regulation of SCF E3 ligases is associated with various human diseases, such as cancers, including skin cancer. In this review, we provide a comprehensive overview of all currently published data to define a promoting role of SCF E3 ligases in the development of skin cancer. The future directions in this area of research are also discussed with an ultimate goal to develop small molecule inhibitors of SCF E3 ligases as a novel approach for the treatment of human skin cancer. Furthermore, altered components or substrates of SCF E3 ligases may also be developed as the biomarkers for early diagnosis or predicting prognosis.
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