Deubiquitinases in the regulation of NF-κB signaling

Cell Res. 2011 Jan;21(1):22-39. doi: 10.1038/cr.2010.166. Epub 2010 Nov 30.


Nuclear factor-kappa B (NF-κB) is a critical regulator of multiple biological functions including innate and adaptive immunity and cell survival. Activation of NF-κB is tightly regulated to preclude chronic signaling that may lead to persistent inflammation and cancer. Ubiquitination of key signaling molecules by E3 ubiquitin ligases has emerged as an important regulatory mechanism for NF-κB signaling. Deubiquitinases (DUBs) counteract E3 ligases and therefore play a prominent role in the downregulation of NF-κB signaling and homeostasis. Understanding the mechanisms of NF-κB downregulation by specific DUBs such as A20 and CYLD may provide therapeutic opportunities for the treatment of chronic inflammatory diseases and cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • DNA-Binding Proteins
  • Deubiquitinating Enzyme CYLD
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology
  • NF-kappa B / metabolism*
  • NF-kappa B / physiology
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology
  • Signal Transduction
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Suppressor Proteins / metabolism
  • Tumor Suppressor Proteins / physiology
  • Ubiquitin / metabolism*
  • Ubiquitination


  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • Ubiquitin
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3