title: Immune defects caused by mutations in the ubiquitin system.
abstract: 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.
authors.affiliation: Ruth Children Hospital, Rambam Health Campus, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: etzioni@rambam.health.gov.il.
authors.forename: Amos
authors.initials: A
authors.lastname: Etzioni
authors.affiliation: Technion Integrated Cancer Center (TICC), Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
authors.affiliation: Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Pikarsky
mesh_terms: D000818:Animals; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D009154:Mutation; D025801:Ubiquitin / Q000235:genetics / Q000276:immunology; D054875:Ubiquitination / Q000235:genetics / Q000276:immunology
chemical_list: D025801:Ubiquitin
keywords: Ubiquitin; immunodeficiency; nuclear factor κB