Immune defects caused by mutations in the ubiquitin system

Amos Etzioni*, Aaron Ciechanover, Eli Pikarsky

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


The importance of the ubiquitin system in health and disease has been widely recognized in recent decades, with better understanding of the various components of the system and their function. Ubiquitination, which is essential to almost all biological processes in eukaryotes, was also found to play an important role in innate and adaptive immune responses. Thus it is not surprising that mutations in genes coding for components of the ubiquitin system cause immune dysregulation. The first defect in the system was described 30 years ago and is due to mutations in the nuclear factor κB (NF-κB) essential modulator, a key regulator of the NF-κB pathway. With use of novel sequencing techniques, many additional mutations in different genes involved in ubiquitination and related to immune system function were identified. This can be clearly illustrated in mutations in the different activation pathways of NF-κB, which result in aberrations in production of various proinflammatory cytokines. The inherited diseases typically manifest with immunodeficiency, autoimmunity, or autoinflammation. In this perspective we provide a short description of the ubiquitin system, with specific emphasis given to its role in the immune system. The various immunodeficiency conditions identified thus far in association with defective ubiquitination are discussed in more detail.

Original languageAmerican English
Pages (from-to)743-753
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Issue number3
StatePublished - Mar 2017

Bibliographical note

Publisher Copyright:
© 2017 American Academy of Allergy, Asthma & Immunology


  • Ubiquitin
  • immunodeficiency
  • nuclear factor κB


Dive into the research topics of 'Immune defects caused by mutations in the ubiquitin system'. Together they form a unique fingerprint.

Cite this