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Chapter Category: Cell Biology
From the book The Multiple Therapeutic Targets of A20
The Biology of A20-Binding Inhibitors of NF-κB activation (ABINs)
Lynn Verstrepen, Isabelle Carpentier and Rudi Beyaert
The family of A20‑Binding Inhibitors of NF‑κB (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‑κB activation. ABIN family members have limited sequence homology in a number of short regions that mediate A20‑binding, ubiquitin‑binding, and NF‑κB 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‑κB‑activating stimuli, suggesting a role for these ABINs in a negative feedback regulation of NF‑κB 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.
- ISBN: TBA
- Publication date: August 15, 2013
- Series: Special Books
The Multiple Therapeutic Targets of A20
Edited by: Christiane Ferran
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The Biology of A20-Binding Inhibitors of NF-κB activation (ABINs)
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