Ubiquitination-mediated degradation of cell cycle-related proteins by F-box proteins

Int J Biochem Cell Biol. 2016 Apr;73:99-110. doi: 10.1016/j.biocel.2016.02.005. Epub 2016 Feb 6.

Abstract

F-box proteins, subunits of SKP1-cullin 1-F-box protein (SCF) type of E3 ubiquitin ligase complexes, have been validated to play a crucial role in governing various cellular processes such as cell cycle, cell proliferation, apoptosis, migration, invasion and metastasis. Recently, a wealth of evidence has emerged that F-box proteins is critically involved in tumorigenesis in part through governing the ubiquitination and subsequent degradation of cell cycle proteins, and dysregulation of this process leads to aberrant cell cycle progression and ultimately, tumorigenesis. Therefore, in this review, we describe the critical role of F-box proteins in the timely regulation of cell cycle. Moreover, we discuss how F-box proteins involve in tumorigenesis via targeting cell cycle-related proteins using biochemistry studies, engineered mouse models, and pathological gene alternations. We conclude that inhibitors of F-box proteins could have promising therapeutic potentials in part through controlling of aberrant cell cycle progression for cancer therapies.

Keywords: Cancer; Cell cycle; Degradation; F-box protein; UPS; Ubiquitination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Ubiquitination / physiology

Substances

  • Cell Cycle Proteins
  • F-Box Proteins