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The Biology of A20-Binding Inhibitors of NF-κB Activation (ABINS)

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Book cover The Multiple Therapeutic Targets of A20

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 809))

Abstract

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 anegative feedbackregulation 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 overexpressionreduces 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.

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Authors and Affiliations

  1. Department of Molecular Biology, Ghent University, Zwijnaarde, Belgium

    Lynn Verstrepen, Isabelle Carpentier & Rudi Beyaert

  2. Department for Molecular Biomedical Research, Unit of Molecular Signal Transduction in Inflammation, VIB, Zwijnaarde, Belgium

    Lynn Verstrepen, Isabelle Carpentier & Rudi Beyaert

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  1. Lynn Verstrepen
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  2. Isabelle Carpentier
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  3. Rudi Beyaert
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Correspondence to Rudi Beyaert .

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Editors and Affiliations

  1. Department of Surgery, Division of Vascular and Endovascular Surgery, Center for Vascular Biology Research, Boston, Massachusetts, USA

    Christiane Ferran MD, PhD

  2. The Transplant Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Christiane Ferran MD, PhD

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Verstrepen, L., Carpentier, I., Beyaert, R. (2014). The Biology of A20-Binding Inhibitors of NF-κB Activation (ABINS). In: Ferran, C. (eds) The Multiple Therapeutic Targets of A20. Advances in Experimental Medicine and Biology, vol 809. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0398-6_2

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