FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase
FAN, a novel WD-repeat protein, couples the p55 TNF-receptor to neutral sphingomyelinase
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DOI：
10.1016/s0092-8674(00)80169-5
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发表时间：
1996-09-20
期刊：
影响因子：
64.5
通讯作者：
Kronke, M
中科院分区：
文献类型：
--
作者：
AdamKlages, S;Adam, D;Kronke, M
通过55 kDa肿瘤坏死因子受体(TNF-R55)启动的细胞内信号事件似乎依赖于与肿瘤坏死因子-R55的特定胞质结构域相互作用的蛋白质中间体。通过酵母相互作用陷阱系统和多肽扫描文库的结合，已经鉴定出新的WD-Repeat蛋白Fan，它特异性地与肿瘤坏死因子-R55的细胞质九个氨基酸结合基序结合。该区域已被认为是一个独特的功能结构域，对中性鞘磷脂酶(N-sMase)的激活既是必需的，也是充分的。全长FAN的过表达增强了肿瘤坏死因子处理的细胞中N-SMase的活性，而FAN的截短突变体产生了明显的负面影响。这些数据表明，Fan通过N-sMase调节神经酰胺的产生，这是肿瘤坏死因子信号转导的关键步骤。
The initiation of intracellular signaling events through the 55 kDa tumor necrosis factor-receptor (TNF-R55) appears to depend on protein intermediates that interact with specific cytoplasmic domains of TNF-R55. By combined use of the yeast interaction trap system and a peptide scanning library, the novel WD-repeat protein FAN has been identified, which specifically binds to a cytoplasmic nine amino acid binding motif of TNF-R55. This region has been previously recognized as a distinct functional domain that is both required and sufficient for the activation of neutral sphingomyelinase (N-SMase). Overexpression of full-length FAN enhanced N-SMase activity in TNF-treated cells, while truncated mutants of FAN produced dominant negative effects. The data suggest that FAN regulates ceramide production by N-SMase, which is a crucial step in TNF signaling.