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ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling
Open accessAbstract
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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“For TNIP1, its gene product (TNF-α-induced protein 3-interacting protein 1) is involved in the inhibition of the TNF-α signaling pathway and nuclear factor κB activation/translocation33.”
From New insights into the genetic etiology of Alzheimer’s disease and related dementias (2022) · cites this paper as [33]
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Metadata
- 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)
- 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
- 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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