多 (ADP-ribose) 聚合酶1通过调节p38 MAPK活动来促进HuR/ELAVL1细胞质局部化和炎症基因表达
Xingyue Fu1, Jiaqi Zhang1, Keke Sun1
1The Key Laboratory of Molecular Epigenetics of the Ministry of Education, School of Life Science, Northeast Normal University, Changchun, 130024, Jilin, China.
Cellular and molecular life sciences : CMLS
|June 9, 2024
概括
多 (ADP-ribose) 聚合酶1 (PARP1) 和p38激酶调节RNA结合蛋白HuR. PARP1通过p38作用,增强HuRR.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 细胞因子/化学因子mRNA循环的转录后调节对于免疫反应至关重要.
- 人类抗原R (HuR) 的RNA结合蛋白是炎症相关的mRNA的关键调节者.
- 胡尔的功能是通过翻译后修改来调节的,影响其局部化和mRNA稳定能力.
研究的目的:
- 阐明聚 (ADP-ribose) 聚合酶1 (PARP1) 和p38基激活蛋白激酶 (MAPKs) 之间控制HuR功能的特定调节和交叉机制.
- 研究PARP1和p38 MAPK如何协同调节细胞质中HuR的积累和与炎症相关的mRNA的稳定.
主要方法:
- 在炎症条件下研究了PARP1和p38 MAPK之间的相互作用.
- 分析了PARP1对p38的多 (ADP-ribosyl) 化 (PARylation),以及它对p38核定位和活性的影响.
- 研究了p38介导的HuR在血清197中的酸化在细胞质转移和mRNA稳定中的作用.
主要成果:
- PARP1通过p38 MAPKs起作用,以协同促进HuR的细胞质积累并稳定与炎症相关的mRNAs.
- p38 MAPKs与自PARylated PARP1 结合,导致p38 PARylation,从而增强p38的核保留和活性.
- 通过PARP1对HuR的PARylation促进了p38介导的酸化在血清197,增加了HuR的转移到细胞质和随后的mRNA稳定.
结论:
- PARP1和p38 MAPKs形成了一个关键的调节轴,控制HuR在炎症期间的转录后基因沉默中的作用.
- 这一途径突出了PARP1和p38 MAPK之间在调节炎症基因表达中的交叉通话的新机制.
- 了解这种调节网络为炎症性疾病提供了潜在的治疗点.
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