Linear ubiquitin chains: NF-κB signalling, cell death and beyond

Nat Rev Mol Cell Biol. 2014 Aug;15(8):503-8. doi: 10.1038/nrm3836. Epub 2014 Jul 9.


Ubiquitylation is a versatile post-translational modification. Met1-linked linear ubiquitin chains are involved in nuclear factor-κB signalling and cell death, and dysfunctions in linear ubiquitylation underlie chronic inflammation. Recent identification of deubiquitylating enzymes and binding domains that are specific for linear ubiquitin chains suggests new physiological roles for linear ubiquitin chains. Moreover, the ligase required for linear ubiquitylation has a crucial role in the pathogenesis of some malignancies. Structural and functional analyses of the conjugation and deconjugation of linear ubiquitin chains have enabled the development of new probes to study the roles of linear chain ubiquitylation.

Publication types

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

MeSH terms

  • Animals
  • Cell Death / genetics
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism*
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Protein Processing, Post-Translational / genetics
  • Signal Transduction / physiology
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination* / genetics


  • NF-kappa B
  • Ubiquitin
  • Ubiquitin-Protein Ligases