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Regulation of NF‐κB by deubiquitinases
Author(s) -
Harhaj Edward W.,
Dixit Vishva M.
Publication year - 2012
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2012.01100.x
Subject(s) - ubiquitin , deubiquitinating enzyme , biology , microbiology and biotechnology , nf κb , regulator , proteasome , iκb kinase , signal transduction , nfkb1 , autophagy , innate immune system , genetics , transcription factor , gene , receptor , apoptosis
Summary: The nuclear factor‐κB (NF‐κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63‐linked polyubiquitination plays a key regulatory role in NF‐κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin‐binding domains. Ubiquitination is balanced by deubiquitinases that cleave polyubiquitin chains and oppose the function of E3 ubiquitin ligases. Deubiquitinases therefore play an important role in the termination of NF‐κB signaling and the resolution of inflammation. In this review, we focus on NF‐κB regulation by deubiquitinases with an emphasis on A20 and CYLD. Deubiquitinases and the ubiquitin/proteasome components that regulate NF‐κB may serve as novel therapeutic targets for inflammatory diseases and cancer.