Regulatory functions of ubiquitination in the immune system

Nat Immunol. 2002 Jan;3(1):20-6. doi: 10.1038/ni0102-20.


Protein modification via covalent attachment of ubiquitin has emerged as one of the most common regulatory processes in all eukaryotes; it is possibly second only to phosphorylation. In fact, ubiquitination and phosphorylation have much in common: both occur rapidly--often in response to an extracellular signal--and both are quickly reversed by a large set of dedicated enzymes termed deubiquitination enzymes and phosphatases, respectively. In addition, these two protein-modification events often cooperate in mobilizing a particular cellular pathway. Traditionally, ubiquitination has been associated with proteolytic events, mostly in conjunction with the 26S proteosome. Recently, however, ubiquitination has been implicated in other regulatory mechanisms. Some involve proteosome-independent protein degradation, whereas others are entirely proteolysis-independent, ranging from protein kinase activation to translation control. Therefore, it is not surprising that the ever-evolving immune system is an excellent mirror for the multiple roles played by ubiquitination within an organism.

Publication types

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

MeSH terms

  • Animals
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation
  • Humans
  • I-kappa B Proteins*
  • Immune System / physiology*
  • Interleukin-1 / physiology
  • Ligases / physiology
  • Models, Biological
  • Multienzyme Complexes / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • NF-kappa B p50 Subunit
  • Phosphorylation
  • Proteasome Endopeptidase Complex
  • Protein Precursors / metabolism
  • Protein Processing, Post-Translational / physiology*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-cbl
  • Signal Transduction
  • Transcription, Genetic
  • Ubiquitin / physiology*
  • Ubiquitin-Conjugating Enzymes
  • Ubiquitin-Protein Ligases
  • src Homology Domains


  • DNA-Binding Proteins
  • I-kappa B Proteins
  • Interleukin-1
  • Multienzyme Complexes
  • NF-kappa B
  • NF-kappa B p50 Subunit
  • NFKBIA protein, human
  • Protein Precursors
  • Proto-Oncogene Proteins
  • Ubiquitin
  • NF-KappaB Inhibitor alpha
  • Ubiquitin-Conjugating Enzymes
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Ligases
  • CBL protein, human