The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN.
The zinc finger protein A20 inhibits TNF-induced NF-kappaB-dependent gene expression by interfering with an RIP- or TRAF2-mediated transactivation signal and directly binds to a novel NF-kappaB-inhibiting protein ABIN.
复制标题
DOI：
10.1083/jcb.145.7.1471
复制
发表时间：
1999-06-28
期刊：
影响因子：
--
通讯作者：
Beyaert R
中科院分区：
文献类型：
--
作者：
Heyninck K;De Valck D;Vanden Berghe W;Van Criekinge W;Contreras R;Fiers W;Haegeman G;Beyaert R
锌指蛋白A20是一种肿瘤坏死因子（TNF）和白细胞介素1（IL-1）诱导的蛋白质，负性调节核因子-κ B（NF-κB）依赖性基因表达。然而，A20发挥这种作用的分子机制仍不清楚。我们发现，A20不抑制TNF诱导的核转位和NF-κB B的DNA结合，尽管它完全阻止TNF诱导的NF-κ B依赖性报告基因的激活，以及TNF诱导的IL-6和粒细胞巨噬细胞集落刺激因子基因的表达。此外，由TNF受体相关蛋白TNF受体相关死亡结构域蛋白（TRADD）、受体相互作用蛋白（RIP）和TNF受体相关因子2（TRAF 2）过表达诱导的NF-κB活化也受到A20表达的抑制，而由NF-κ B诱导激酶（NIK）或人T细胞白血病病毒1型（HTLV-1）Tax过表达诱导的NF-κB活化不受影响。这些结果表明，A20通过干扰一种新的TNF诱导和RIP或TRAF 2介导的途径抑制NF-κ B依赖性基因表达，该途径不同于NIK-IκB激酶途径，并特异性参与NF-κB的反式激活。通过酵母双杂交筛选，我们发现A20与一种新的蛋白ABIN结合，该蛋白模拟了A20过表达时对NF-κB的抑制作用，这表明A20的作用是通过其与这种NF-κB抑制蛋白ABIN的相互作用来介导的。
The zinc finger protein A20 is a tumor necrosis factor (TNF)– and interleukin 1 (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B (NF-κB)–dependent gene expression. However, the molecular mechanism by which A20 exerts this effect is still unclear. We show that A20 does not inhibit TNF- induced nuclear translocation and DNA binding of NF-κB, although it completely prevents the TNF- induced activation of an NF-κB–dependent reporter gene, as well as TNF-induced IL-6 and granulocyte macrophage–colony stimulating factor gene expression. Moreover, NF-κB activation induced by overexpression of the TNF receptor–associated proteins TNF receptor–associated death domain protein (TRADD), receptor interacting protein (RIP), and TNF recep- tor–associated factor 2 (TRAF2) was also inhibited by expression of A20, whereas NF-κB activation induced by overexpression of NF-κB–inducing kinase (NIK) or the human T cell leukemia virus type 1 (HTLV-1) Tax was unaffected. These results demonstrate that A20 inhibits NF-κB–dependent gene expression by interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is different from the NIK–IκB kinase pathway and that is specifically involved in the transactivation of NF-κB. Via yeast two-hybrid screening, we found that A20 binds to a novel protein, ABIN, which mimics the NF-κB inhibiting effects of A20 upon overexpression, suggesting that the effect of A20 is mediated by its interaction with this NF-κB inhibiting protein, ABIN.
登录
查看更多内容
影响因子：
4.8
作者：
Chu, ZL;DiDonato, JK;Ballard, DW
通讯作者：
Ballard, DW
影响因子：
3.5
作者：
DeValck, D;Heyninck, K;Fiers, W
通讯作者：
Fiers, W
影响因子：
11.4
作者：
Beyaert, R;Cuenda, A;Fiers, W
通讯作者：
Fiers, W
影响因子：
64.5
作者：
HSU, HL;XIONG, J;GOEDDEL, DV
通讯作者：
GOEDDEL, DV
影响因子：
64.8
作者：
HENKEL, T;MACHLEIDT, T;BAEUERLE, PA
通讯作者：
BAEUERLE, PA