Cited by 180NF-κB Signaling PathwaysImmune Response and InflammationSignaling Pathways in Disease

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ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling

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Verstrepen, Lynn, Carpentier, Isabelle, Verhelst, Kelly, Beyaert, Rudi·2009·Biochemical Pharmacology

DOI 10.1016/j.bcp.2009.02.009

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Abstract

ABINs have been described as three different proteins (ABIN-1, ABIN-2, ABIN-3) that bind the ubiquitin-editing nuclear factor-kappaB (NF-kappaB) inhibitor protein A20 and which show limited sequence homology. Overexpression of ABINs inhibits NF-kappaB activation by tumor necrosis factor (TNF) and several other stimuli. Similar to A20, ABIN-1 and ABIN-3 expression is NF-kappaB dependent, implicating a potential role for the A20/ABIN complex in the negative feedback regulation of NF-kappaB activation. Adenoviral gene transfer of ABIN-1 has been shown to reduce NF-kappaB activation in mouse liver and lungs. However, ABIN-1 as well as ABIN-2 deficient mice exhibit only slightly increased or normal NF-kappaB activation, respectively, possibly reflecting redundant NF-kappaB inhibitory activities of multiple ABINs. Other functions of ABINs might be non-redundant. For example, ABIN-1 shares with A20 the ability to inhibit TNF-induced apoptosis and as a result ABIN-1 deficient mice die during embryogenesis due to TNF-dependent fetal liver apoptosis. On the other hand, ABIN-2 is required for optimal TPL-2 dependent extracellularly regulated kinase activation in macrophages treated with TNF or Toll-like receptor ligands. ABINs have recently been shown to contain an ubiquitin-binding domain that is essential for their NF-kappaB inhibitory and anti-apoptotic activities. In this context, ABINs were proposed to function as adaptors between ubiquitinated proteins and other regulatory proteins. Alternatively, ABINs might disrupt signaling complexes by competing with other ubiquitin-binding proteins for the binding to specific ubiquitinated targets. Altogether, these findings implicate an important role for ABINs in the regulation of immunity and tissue homeostasis.

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See all 180

Authors: Verstrepen, L., Carpentier, I., Verhelst, K., & Beyaert, R.
Affiliations: Vlaams Instituut voor Biotechnologie (BE)
Corresponding author: Beyaert, Rudi
ORCID: Beyaert, Rudi
Venue: Biochemical Pharmacology
Publisher: Elsevier BV
Published: 2009-07
Volume: 78
Issue: 2
Pages: 105-114
ISSN: 0006-2952 (ISSN-L)
DOI: 10.1016/j.bcp.2009.02.009
OpenAlex: W2010220327
Cited by: 180
References: 76
Citations by year: 2026: 5 · 2025: 5 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 6 · 2020: 10 · 2019: 5 · 2018: 16 · 2017: 16 · 2016: 18 · 2015: 11 · 2014: 12 · 2013: 15 · 2012: 12
FWCI: 0.94
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Biochemical Pharmacology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Ghent University Academic Bibliography (Ghent University) (submittedVersion)
Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
Funders: Agentschap voor Innovatie door Wetenschap en Technologie
Universiteit Gent
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: Abin, A20, NF-κB, ubiquitin-binding domain, TNF-induced apoptosis, negative feedback regulation, ERK activation, macrophages, embryonic lethality, immunity, tissue homeostasis, ubiquitinated proteins
MeSH terms: Tumor Necrosis Factor alpha-Induced Protein 3, Amino Acid Sequence, Animals, DNA-Binding Proteins, Humans, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Proteins, Signal Transduction, NF-kappa B, Apoptosis, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins

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ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling

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