The regulation of TGF-β/SMAD signaling by protein deubiquitination

Protein Cell. 2014 Jul;5(7):503-17. doi: 10.1007/s13238-014-0058-8. Epub 2014 Apr 23.

Abstract

Transforming growth factor-β (TGF-β) members are key cytokines that control embryogenesis and tissue homeostasis via transmembrane TGF-β type II (TβR II) and type I (TβRI) and serine/threonine kinases receptors. Aberrant activation of TGF-β signaling leads to diseases, including cancer. In advanced cancer, the TGF-β/SMAD pathway can act as an oncogenic factor driving tumor cell invasion and metastasis, and thus is considered to be a therapeutic target. The activity of TGF-β/SMAD pathway is known to be regulated by ubiquitination at multiple levels. As ubiquitination is reversible, emerging studies have uncovered key roles for ubiquitin-removals on TGF-β signaling components by deubiquitinating enzymes (DUBs). In this paper, we summarize the latest findings on the DUBs that control the activity of the TGF-β signaling pathway. The regulatory roles of these DUBs as a driving force for cancer progression as well as their underlying working mechanisms are also discussed.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Molecular Targeted Therapy
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction*
  • Smad Proteins / physiology*
  • Transforming Growth Factor beta / physiology*
  • Ubiquitin Thiolesterase / metabolism
  • Ubiquitin-Specific Proteases
  • Ubiquitination*

Substances

  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta
  • USP4 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases