SHARPIN 是 NF-κB 激活线性泛素链组装复合体的组成部分
Fuminori Tokunaga1, Tomoko Nakagawa, Masaki Nakahara
1Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Nature
|April 2, 2011
概括
SHARPIN被确定为线性无素链组合复合体 (LUBAC) 的关键组成部分,这对NF-κB激活至关重要. 这一发现揭示了与LUBAC功能障碍相关的免疫疾病.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 慢性增殖性皮肤炎 (cpdm) 的小鼠表现出皮肤炎和免疫缺陷,反映了人类的X链接超IgM综合征.
- 沙宾基因的突变导致cpdm表型,沙宾蛋白与LUBAC成分相似.
研究的目的:
- 确定SHARPIN在线性无素链组装复合体 (LUBAC) 中的作用.
- 阐明Sharpin在LUBAC中的功能及其对NF-κB激活的影响.
主要方法:
- 生物化学分析以确定SHARPIN作为LUBAC成分.
- 在小鼠胚胎纤维细胞和来自cpdm小鼠的B细胞中评估NF-κB激活.
- 研究SHARPIN删除对LUBAC水平和TNF-α/CD40介导的NF-κB信号传递的影响.
主要成果:
- SHARPIN被证实是LUBAC的组成部分,与HOIL-1L和HOIP一起.
- 含有SHARPIN的复合物调解NEMO的线性无化和激活的NF-κB.
- 缺少SHARPIN显著降低了LUBAC水平,并减弱了NF-κB的激活.
结论:
- LUBAC被重新定义为一个由SHARPIN,HOIL-1L和HOIP组成的复合体.
- SHARPIN在LUBAC中的作用对于有效的NF-κB激活至关重要.
- 通过LUBAC介导的NF-κB激活的失调可能导致各种疾病.
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