通过PARP12介导的单-ADP-ribosylation作为死和死的检查点
Xin Huang1,2,3, Fangxia Li2,4, Lin Liu1,2,3
1Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, China.
概括
聚基聚合酶12 (PARP12) 通过修改 RIPK1 和 RIPK3.3 来调节细胞死亡途径. 缺乏PARP12可促进抗病毒反应并减少亡.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 细胞死亡的分子机制
背景情况:
- 亡和亡是不同的细胞死亡途径.
- 受体相互作用蛋白激酶1 (RIPK1) 是这两种途径的关键调节者.
- 翻译后的RIPK1修改控制其活动和复杂的形成.
研究的目的:
- 调查PARP12在调节RIPK1和RIPK3.3中的Poly ((ADP-ribose) 聚合酶12的作用.
- 阐明PARP12影响亡和亡的机制.
- 确定PARP12对细胞抗病毒反应的影响.
主要方法:
- 在IFNγ和TNFα刺激的细胞中研究了PARP12与RIPK1和RIPK3的相互作用.
- 分析了PARP12缺乏对RIPK1激酶激活,RIPK1/RIPK3复合体形成和RIPK1/caspase-8结合的影响.
- 评估了PARP12缺乏对干扰素刺激基因 (ISG) 和小鼠流感A病毒感染的影响.
主要成果:
- PARP12 催化了 RIPK1 和 RIPK3.3 的单-ADP 核糖化 (MARylation).
- PARP12 缺乏抑制了 RIPK1 激酶激活和 RIPK1/RIPK3 相互作用,降低了亡.
- 缺乏PARP12增强了RIPK1/caspase-8结合,使细胞对细胞亡敏感,并促进ISG的表达,从而提供对流感A病毒的保护.
结论:
- PARP12充当细胞检查点,调节RIPK1活动以促进亡并抑制IFN诱导后的亡.
- PARP12是细胞抗病毒反应的重要调节剂.
- 缺乏PARP12可以保护人免受病毒感染.
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