The emerging complexity of protein ubiquitination

Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937.

Abstract

Protein ubiquitination and protein phosphorylation are two fundamental regulatory post-translational modifications controlling intracellular signalling events. However, the ubiquitin system is vastly more complex compared with phosphorylation. This is due to the ability of ubiquitin to form polymers, i.e. ubiquitin chains, of at least eight different linkages. The linkage type of the ubiquitin chain determines whether a modified protein is degraded by the proteasome or serves to attract proteins to initiate signalling cascades or be internalized. The present review focuses on the emerging complexity of the ubiquitin system. I review what is known about individual chain types, and highlight recent advances that explain how the ubiquitin system achieves its intrinsic specificity. There is much to be learnt from the better-studied phosphorylation system, and many key regulatory mechanisms underlying control by protein phosphorylation may be similarly employed within the ubiquitin system. For example, ubiquitination may have important allosteric roles in protein regulation that are currently not appreciated.

Publication types

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

MeSH terms

  • Humans
  • Lysine / metabolism
  • Models, Molecular
  • Phosphorylation
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Processing, Post-Translational*
  • Protein Structure, Tertiary
  • Signal Transduction / physiology
  • Ubiquitin* / chemistry
  • Ubiquitin* / genetics
  • Ubiquitin* / metabolism
  • Ubiquitination

Substances

  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • Lysine