ABINs: A20 binding inhibitors of NF-kappa B and apoptosis signaling

作者：Verstrepen Lynn; Carpentier Isabelle; Verhelst Kelly; Beyaert Rudi^*

来源：Biochemical Pharmacology, 2009, 78(2): 105-114.

DOI：10.1016/j.bcp.2009.02.009

• Inflammation
• NF-kappa B
• Apoptosis
• ABIN
• A20

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.

• 出版日期2009-7-15