期刊
BIOCHEMICAL PHARMACOLOGY
卷 78, 期 2, 页码 105-114出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2009.02.009
关键词
Inflammation; NF-kappa B; Apoptosis; ABIN; A20
资金
- Interuniversitaire Attractiepolen [IAP6/18]
- FWO-Vlaanderen [3G01 0505]
- Foundation against Cancer
- Emmanuel van der Schueren Foundation
- Geconcerteerde Onderzoeksacties [01 G06136]
ABINs have been described as three different proteins (ABIN-1, ABIN-2, ABIN-3) that bind the ubiquitin-editing nuclear factor-kappa B (NF-kappa B) inhibitor protein A20 and which show limited sequence homology. Overexpression of ABINs inhibits NF-kappa B activation by tumor necrosis factor (TNF) and several other stimuli. Similar to A20, ABIN-1 and ABIN-3 expression is NF-kappa B dependent, implicating a potential role for the A20/ABIN complex in the negative feedback regulation of NF-kappa B activation. Adenoviral gene transfer of ABIN-I has been shown to reduce NF-kappa B activation in mouse liver and lungs. However, ABIN-1 as well as ABIN-2 deficient mice exhibit only slightly increased or normal NF-kappa B activation, respectively, possibly reflecting redundant NF-kappa B inhibitory activities of multiple ABINs. Other functions of ABINs might be non-redundant. For example, ABIN-I 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-kappa B 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. (C) 2009 Elsevier Inc. All rights reserved.
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