在p62体中由干扰素诱导的PARP14介导的ADP-ribosylation需要全素-蛋白酶体系统
Rameez Raja1, Banhi Biswas1, Rachy Abraham1
1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
The EMBO journal
|April 8, 2025
概括
干扰素通过PARP14介导的ADP-ribosylation触发细胞凝结物的形成. 这些结构被称为p62体,依赖于无素-蛋白酶体系统,而不是自.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 生物分子凝聚物是没有膜的器官,可以动态调节细胞过程.
- 干扰素信号诱导ADP-ribosylation (ADPr),一种在细胞凝结物中丰富的修饰,但具体的凝结物和涉及的酶是未知的.
研究的目的:
- 为了确定主体ADP-ribosyltransferase负责干扰素诱导的ADPr.
- 描述与ADPr.丰富的冷凝液的性质和形成机制.
主要方法:
- 研究了Poly ((ADP-ribose) 聚合酶14 (PARP14) 在干扰素诱导的ADPr和凝结物形成中的作用.
- 利用免疫光显微镜来评估PARP14,ADPR和其他细胞组件的同位化.
- 研究了基因淘汰和药物抑制剂对凝结物的形成和稳定性的影响.
主要成果:
- 干扰素通过转录激活PARP14来诱导ADPr,这对于凝结物形成至关重要.
- 鉴定到的冷凝物是p62体,含有p62,NBR1,TAX1BP1和多比基因链,但没有LC3B.
- 凝析物形成取决于无处不在和蛋白酶体活动,并且独立于自.
结论:
- 干扰素信号激活PARP14,以在p62体内调解ADP-ribosylation. 在p62体内调解ADP-ribosylation.
- 这些干扰素诱导的凝聚物受到乌比奎-蛋白酶体系统的调节,突出了一个新的非自途径.
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