Linear ubiquitination: a newly discovered regulator of cell signalling

Trends Biochem Sci. 2013 Feb;38(2):94-102. doi: 10.1016/j.tibs.2012.11.007. Epub 2013 Jan 17.


Ubiquitination is a post-translational modification that creates versatility in cell signalling, in part because eight biochemically different inter-ubiquitin linkages can be formed through the seven internal lysine residues of ubiquitin or its amino-terminal methionine. The latter, referred to as linear or M1 linkage, is created by the linear ubiquitin chain assembly complex (LUBAC). Previously, K63 linkages were thought to be exclusively responsible for ubiquitin-mediated nondegradative functions. It now emerges, however, that M1 ubiquitination is crucial in various pathways, and that generation of a physiological signalling output requires cooperation between different ubiquitin linkage types. Here, we review the currently known functions of LUBAC and M1 ubiquitination, discuss promising future research directions into their functions, and how this may reveal novel therapeutic opportunities for diseases with perturbed linear ubiquitination.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Lysine / metabolism
  • Methionine / metabolism
  • Models, Biological
  • Multiprotein Complexes / metabolism*
  • Signal Transduction*
  • Ubiquitin / metabolism*
  • Ubiquitination*


  • Multiprotein Complexes
  • Ubiquitin
  • Methionine
  • Lysine