促炎性刺激会诱导IKKalpha介导的PIAS1酸化,以限制炎症和免疫力
Bin Liu1, Yonghui Yang, Vasili Chernishof
1Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
Cell
|June 2, 2007
概括
炎症信号激活IKKalpha以化PIAS1,这是一个通过阻断基因激活来抑制炎症的关键调节器. 这种酸化对于PIAS1是必不可少的.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 转录条例 转录条例 转录条例
背景情况:
- 炎症刺激向核发出信号以限制炎症的机制尚未完全理解.
- 激活STAT1的蛋白抑制剂 (PIAS1) 是一种转录调节剂,具有小的泛素相关修饰剂 (SUMO) E3结合酶活性,通过阻断NF-kappaB和STAT1与基因促进体结合来抑制免疫反应.
研究的目的:
- 阐明炎症刺激导致核抑制炎症的信号通路.
- 研究PIAS1酸化在调节炎性基因激活中的作用.
主要方法:
- 利用突变研究来评估PIAS1酸化在Ser90.0的功能.
- 采用了TNF治疗,并分析了野生类型和突变PIAS1与基因促进者的关联.
- 研究了IKKalpha,IKKbeta和PIAS1.1之间的体内相互作用.
主要成果:
- 在响应炎症刺激时,PIAS1在Ser90上快速酸化.
- 化Ser90对PIAS1的转录抑制活动至关重要.
- 野生类型的PIAS1,但不是Ser90A突变,在TNF治疗时与NF-kappaB向基因促进体结合.
- IKKalpha,而不是IKKbeta,与PIAS1相互作用,并调解Ser90酸化,这取决于PIAS1的SUMO结合酶活性.
结论:
- 确定了一个信号通路,炎症刺激激活IKKalpha.
- IKKalpha 在Ser90.0 处调解PIAS1的化,而这种化依赖于sumoylation.
- 这一过程导致PIAS1.1立即抑制炎症基因激活.
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