F-box proteins and cancer: an update from functional and regulatory mechanism to therapeutic clinical prospects

Theranostics. 2020 Mar 4;10(9):4150-4167. doi: 10.7150/thno.42735. eCollection 2020.

Abstract

E3 ubiquitin ligases play a critical role in cellular mechanisms and cancer progression. F-box protein is the core component of the SKP1-cullin 1-F-box (SCF)-type E3 ubiquitin ligase and directly binds to substrates by various specific domains. According to the specific domains, F-box proteins are further classified into three sub-families: 1) F-box with leucine rich amino acid repeats (FBXL); 2) F-box with WD 40 amino acid repeats (FBXW); 3) F-box only with uncharacterized domains (FBXO). Here, we summarize the substrates of F-box proteins, discuss the important molecular mechanism and emerging role of F-box proteins especially from the perspective of cancer development and progression. These findings will shed new light on malignant tumor progression mechanisms, and suggest the potential role of F-box proteins as cancer biomarkers and therapeutic targets for future cancer treatment.

Keywords: E3 ligase; F-box; cancer progression; substrate; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Line, Tumor
  • F-Box Proteins* / antagonists & inhibitors
  • F-Box Proteins* / metabolism
  • Humans
  • Ligands
  • Mice
  • Neoplasms / metabolism*
  • Signal Transduction
  • Ubiquitination

Substances

  • F-Box Proteins
  • Ligands