USP18通过促进气体皮质D的选择性自降解来对抗 Pyroptosis
Liqiu Wang1, Mengqiu Li1, Guangyu Lian1
1MOE Key Laboratory of Gene Function and Regulation, Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, State Key Laboratory of Biocontrol, School of Life Sciences of Sun Yat-sen University, Guangzhou, Guangdong, China.
Research (Washington, D.C.)
|May 23, 2024
概括
乌比基特异性酶18 (USP18) 通过向Gasdermin D (GSDMD) 进行降解来调节热. 这可以防止过度炎症,并通过选择性自控制GSDMD蛋白水平.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 加斯德明D (GSDMD) 是热的关键调解者,这是一个关键的炎症细胞死亡途径,参与宿主防御.
- 失调的热致病有助于炎症性疾病,使得GSDMD成为重要的治疗点.
- 控制GSDMD蛋白水平控制恒温的机制尚未完全理解.
研究的目的:
- 调查基特异性酶18 (USP18) 在调节GSDMD和热的作用.
- 阐明USP18控制GSDMD蛋白质稳定的分子机制.
主要方法:
- 研究了USP18与GSDMD和E3无酸酶MIB2.2.的相互作用.
- 在K168.8处分析了GSDMD的无处不在.
- 研究了选择性自在GSDMD降解中的作用.
- 在体内评估了USP18在LPS诱导的炎症模型中的作用.
主要成果:
- 通过促进GSDMD降解,USP18作为热的负调节剂.
- USP18招募了思维炸弹同类物2 (MIB2) 来在168 lysine上使GSDMD无处不在.
- 乌比基化GSDMD是通过选择性自来降解的目标.
- 在体内,USP18减轻了LPS诱导的炎症.
结论:
- USP18通过一种涉及MIB2介导的无化和选择性自的机制,严格控制GSDMD蛋白水平.
- USP18 作为 pyroptosis 的负调节剂,为炎症性疾病提供潜在的治疗策略.
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