title: The biology of A20-binding inhibitors of NF-kappaB activation (ABINs).
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.
authors.forename: Lynn
authors.initials: L
authors.lastname: Verstrepen
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carpentier
authors.forename: Rudi
authors.initials: R
authors.lastname: Beyaert
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003546:Cysteine Endopeptidases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D044767:Ubiquitin-Protein Ligases; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D003546:Cysteine Endopeptidases; C513261:Tnfaip3 protein, mouse