Differential signaling and tumor necrosis factor receptor-associated factor (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1).
Differential signaling and tumor necrosis factor receptor-associated factor (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1).
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DOI：
10.1084/jem.193.8.943
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发表时间：
2001-04-16
期刊：
影响因子：
--
通讯作者：
Bishop GA
中科院分区：
文献类型：
--
作者：
Brown KD;Hostager BS;Bishop GA
潜伏膜蛋白1（LMP 1）在EB病毒（EBV）转化B细胞中起关键作用，并且似乎模拟组成型活性的CD 40受体。细胞内肿瘤坏死因子（TNF）受体相关因子（TRAF）衔接蛋白，有助于通过CD 40和LMP 1的信号传导，被这两种分子招募到富含脂质的膜筏。然而，我们发现TRAF 2和3随后在CD 40诱导的信号传导后降解，而不是LMP 1诱导的信号传导。这种降解是蛋白酶体依赖性的，需要CD 40直接结合TRAF。使用设计用于直接比较B淋巴细胞中LMP 1和CD 40的胞质结构域的信号传导效力的模型系统，我们发现LMP 1比CD 40更有效地激活c-Jun激酶和核因子κB，并诱导更高水平的几种B细胞效应子功能。这表明LMP 1利用了修饰的CD 40信号通路。不能调节TRAF可能有助于增强LMP 1激活B细胞以及促进B细胞转化的能力。
Latent membrane protein 1 (LMP1) plays a critical role in B cell transformation by Epstein-Barr virus (EBV) and appears to mimic a constitutively active CD40 receptor. Intracellular tumor necrosis factor (TNF) receptor–associated factor (TRAF) adapter proteins, shown to contribute to signaling by both CD40 and LMP1, were recruited by both molecules to lipid-enriched membrane rafts. However, we found that TRAFs 2 and 3 were subsequently degraded after CD40- but not LMP1-induced signaling. This degradation was proteasome-dependent and required direct TRAF binding by CD40. Using a model system designed to directly compare the signaling potency of the cytoplasmic domains of LMP1 and CD40 in B lymphocytes, we found that LMP1 more potently activates c-Jun kinase and nuclear factor κB and induces higher levels of several B cell effector functions than does CD40. This suggests that LMP1 utilizes a modified CD40 signaling pathway. Failure to regulate TRAFs may contribute to the enhanced capacity of LMP1 to activate B cells as well as promote B cell transformation.
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影响因子：
4.4
作者：
Jalukar, SV;Hostager, BS;Bishop, GA
通讯作者：
Bishop, GA
影响因子：
5.4
作者：
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影响因子：
8
作者：
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影响因子：
56.9
作者：
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通讯作者：
BALTIMORE, D
DOI：
10.1073/pnas.93.18.9437
发表时间：
1996-09-03
影响因子：
11.1
作者：
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通讯作者：
Inoue, J