The biology of A20-binding inhibitors of NF-kappaB activation (ABINs)

Adv Exp Med Biol. 2014:809:13-31. doi: 10.1007/978-1-4939-0398-6_2.

Abstract

The family of A20-Binding Inhibitors of NF-kappaB (ABINs) consists of three proteins, ABIN-1, ABIN-2 and ABIN-3, which were originally identified as A20-binding proteins and inhibitors of cytokines and Lipopolysaccharide (LPS) induced NF-kappaB activation. ABIN family members have limited sequence homology in a number of short regions that mediate A20-binding, ubiquitin-binding, and NF-kappaB inhibition. The functional role of A20 binding to ABINs remains unclear, although an adaptor function has been suggested. ABIN-1 and ABIN-3 expression is upregulated when cells are triggered by NF-kappaB-activating stimuli, suggesting a role for these ABINs in a negative feedback regulation of NF-kappaB signaling. Additional ABIN functions have been reported such as inhibition of TNF-induced hepatocyte apoptosis, regulation of HIV-1 replication for ABIN-1, and Tumor Progression Locus 2 (TPL-2)-mediated Extracellular signal-Regulated Kinase (ERK) activation for ABIN-2. In mice, ABIN-1 overexpression reduces allergic airway inflammation and TNF-mediated liver injury, ABIN-2 overexpression delays liver regeneration, and ABIN-3 overexpression partially protects against LPS-induced acute liver failure. Analysis of mice deficient in ABIN-1 or ABIN-2 demonstrates the important immune regulatory function of ABINs. Future studies should clarify the functional implication of the A20-ABIN interaction in supporting ABINs' mechanisms of action.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cysteine Endopeptidases
  • DNA-Binding Proteins / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Protein Binding
  • Sequence Homology, Amino Acid
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Intracellular Signaling Peptides and Proteins
  • NF-kappa B
  • Ubiquitin-Protein Ligases
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Cysteine Endopeptidases
  • Tnfaip3 protein, mouse