Innate immune-directed NF-κB signaling requires site-specific NEMO ubiquitination.
Innate immune-directed NF-κB signaling requires site-specific NEMO ubiquitination.
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先天免疫指导的NF-κB信号传导需要特定地点的Nemo泛素化。
DOI：
10.1016/j.celrep.2013.06.036
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发表时间：
2013-07-25
期刊：
影响因子：
8.8
通讯作者：
Abbott DW
中科院分区：
文献类型：
--
作者：
Jun JC;Kertesy S;Jones MB;Marinis JM;Cobb BA;Tigno-Aranjuez JT;Abbott DW
虽然I κ激酶（IKK）支架蛋白NF-κ B必需调节剂（NEMO）结合多聚泛素链以传递炎症信号，但NEMO本身也响应于多种炎症激动剂而被泛素化。虽然有迹象表明NEMO的多泛素化对于避免炎症性疾病是必不可少的，但NEMO泛素化的体内生理作用尚不清楚。在这项工作中，我们敲入NEMO等位基因，其中两个主要的炎症激动剂诱导的泛素化位点不能被泛素化。我们发现，小鼠与nonubiquitinatable NEMO等位基因显示胚胎致死。杂合子雌性出现炎症性皮肤病变、B细胞数量减少和脾细胞增多。胚胎致死性可以通过在TNFR1 −/−背景下交配来补充，代价是严重的脂肪性肝炎和早期死亡，我们还表明NEMO泛素化是最佳先天免疫信号传导反应所必需的。这些发现表明，NEMO泛素化是至关重要的NF-κ B活性的先天免疫激动剂。
While the I kappa kinase (IKK) scaffolding protein NF-κB essential modulator (NEMO) binds to polyubiquitin chains to transmit inflammatory signals, NEMO itself is also ubiquitinated in response to a variety of inflammatory agonists. Although there have been hints that polyubiquitination of NEMO is essential for avoiding inflammatory disorders, the in vivo physiologic role of NEMO ubiquitination is unknown. In this work, we knock in a NEMO allele in which two major inflammatory agonist-induced ubiquitination sites cannot be ubiquitinated. We show that mice with a nonubiquitinatable NEMO allele display embryonic lethality. Heterozygous females develop inflammatory skin lesions, decreased B cell numbers, and hypercellular spleens. Embryonic lethality can be complemented by mating onto a TNFR1−/− background, at the cost of severe steatohepatitis and early mortality, and we also show that NEMO ubiquitination is required for optimal innate immune signaling responses. These findings suggest that NEMO ubiquitination is crucial for NF-κB activity in response to innate immune agonists.
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DOI：
10.1084/jem.20082152
发表时间：
2009-08-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Beraza N;Malato Y;Sander LE;Al-Masaoudi M;Freimuth J;Riethmacher D;Gores GJ;Roskams T;Liedtke C;Trautwein C
通讯作者：
Trautwein C
影响因子：
5.3
作者：
Yang, Huei-Ting;Papoutsopoulou, Stamatia;Ley, Steven C.
通讯作者：
Ley, Steven C.
影响因子：
50.3
作者：
Luedde, Tom;Beraza, Naiara;Pasparakis, Manolis
通讯作者：
Pasparakis, Manolis
影响因子：
32.4
作者：
Stark GR;Darnell JE Jr
通讯作者：
Darnell JE Jr
Nemo识别二丁素蛋白的结构基础。
影响因子：
16
作者：
Lo, Yu-Chih;Lin, Su-Chang;Rospigliosi, Carla C.;Conze, Dietrich B.;Wu, Chuan-Jin;Ashwell, Jonathan D.;Eliezer, David;Wu, Hao
通讯作者：
Wu, Hao