Regulation of NF-κB by deubiquitinases

Edward W. Harhaj, Vishva M. Dixit

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)107-124
Number of pages18
JournalImmunological reviews
Issue number1
StatePublished - Mar 2012
Externally publishedYes


  • A20
  • CYLD
  • Deubiquitinases
  • Inflammation
  • NF-κB

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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