A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-κB activation
A novel zinc finger protein interacts with receptor-interacting protein (RIP) and inhibits tumor necrosis factor (TNF)- and IL1-induced NF-κB activation
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DOI：
10.1074/jbc.m108675200
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发表时间：
2002-05-03
影响因子：
4.8
通讯作者：
Shu, HB
中科院分区：
文献类型：
--
作者：
Chen, DY;Li, XY;Shu, HB
受体相互作用蛋白（RIP）是一种丝氨酸/苏氨酸蛋白激酶，在肿瘤坏死因子受体-1（TNF-R1）诱导的NF-kappaB激活中发挥重要作用。在酵母双杂交筛选潜在的RIP相互作用的蛋白质，我们确定了锌（锌指蛋白抑制NF-κ B），一种新的蛋白质，特异性与RIP相互作用。ZIN在中间含有四个RING样锌指结构域，在C末端含有一个富含脯氨酸的结构域。在293细胞中，ZIN的过表达以剂量依赖性方式抑制RIP、IKK β、TNF和IL 1诱导的NF-κ B活化。结构域作图实验表明，ZIN的RING样锌指结构域是其与RIP相互作用和抑制RIP介导的NF-κ B活化所必需的。ZIN的过表达也增强RIP和TNF诱导的细胞凋亡。此外，免疫荧光染色表明，ZIN是一种细胞质蛋白，它与RIP共定位。我们的研究结果表明，锌是一种抑制剂的TNF-和IL-1诱导的NF-κ B活化途径。
Receptor-interacting protein (RIP) is a serine/threonine protein kinase that is critically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappaB activation. In a yeast two-hybrid screening for potential RIP-interacting proteins, we identified ZIN (zinc finger protein inhibiting NF-kappaB), a novel protein that specifically interacts with RIP. ZIN contains four RING-like zinc finger domains at the middle and a proline-rich domain at the C terminus. Overexpression of ZIN inhibits RIP-, IKKbeta-, TNF-, and IL1-induced NF-kappaB activation in a dose-dependent manner in 293 cells. Domain mapping experiments indicate that the RING-like zinc finger domains of ZIN are required for its interaction with RIP and inhibition of RIP-mediated NF-kappaB activation. Overexpression of ZIN also potentiates RIP- and TNF-induced apoptosis. Moreover, immunofluorescent staining indicates that ZIN is a cytoplasmic protein and that it colocalizes with RIP. Our findings suggest that ZIN is an inhibitor of TNF- and IL1-induced NF-kappaB activation pathways.