ABINs: A20 binding inhibitors of NF-κB and apoptosis signaling
hgl1990 添加于 2010-7-12 16:59
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Verstrepen L, Carpentier I, Verhelst K, Beyaert R 摘 要
ABINs have been described as three different proteins (ABIN-1, ABIN-2, ABIN-3) that bind the ubiquitin-editing nuclear factor-κB ( NF -κB) inhibitor protein A20 and which show limited sequence homology. Overexpression of ABINs inhibits NF -κB activation by tumor necrosis factor (TNF) and several other stimuli. Similar to A20, ABIN-1 and ABIN-3 expression is NF -κB dependent, implicating a potential role for the A20/ABIN complex in the negative feedback regulation of NF -κB activation. Adenoviral gene transfer of ABIN-1 has been shown to reduce NF -κB activation in mouse liver and lungs. However, ABIN-1 as well as ABIN-2 deficient mice exhibit only slightly increased or normal NF -κB activation, respectively, possibly reflecting redundant NF -κB 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 -κB 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.-
详细资料
- 文献种类:期刊
- 期刊名称: Biochemical Pharmacology
- 期刊缩写: Biochemical Pharmacology
- 期卷页: 2009年 第78卷 第2期 105-114页
- ISBN: 0006-2952
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