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热冲击通过p38 MAPK信号级联诱导HuR依赖的MKP-1后翻译调节
Xiao-Juan Ma1, Zhan Sun1, Yi-Ping Wang1
1Department of Pathophysiology, College of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang 830000, China.
Tissue & cell
|November 20, 2023
概括
热冲击通过人抗原R (HuR) 和p38 MAPK通路稳定了中原激活蛋白激酶酸酶-1 (MKP-1) mRNA. 这项研究揭示了HuRR.
科学领域:
- 分子生物学分子生物学
- 细胞信号传输 细胞信号传输
- 应激反应机制 应激反应机制
背景情况:
- 酸酶是炎症和压力反应的关键调节者.
- 基激活蛋白激酶酸酶-1 (MKP-1) 在热冲击信号传输中至关重要.
- 人类抗原R (HuR) 增强了压力反应蛋白水平,包括MKP-1.
研究的目的:
- 为了研究热冲击诱导的MKP-1mRNA稳定机制.
- 阐明HuR和p38 MAPK通路在这个过程中的作用.
主要方法:
- 热冲击治疗小鼠胚胎纤维细胞 (MEF) 细胞.
- 对MKP-1 mRNA稳定性和HuR与3' UTR结合的分析.
- 基因沉默 (siRNA) 和过度表达 (旗HuR等离子体) 的HuR.
- 抑制p38 MAPK活动.
- 免疫光学来追踪HuR转位.
主要成果:
- 热冲击显著稳定了MEF细胞中的MKP-1mRNA.
- HuR直接与MKP-1 mRNA的富含AU的3' UTR结合.
- 胡尔过度表达增加了MKP-1mRNA的稳定性;胡尔沉默降低了后热冲击.
- p38 MAPK抑制降低了热冲击介导的MKP-1mRNA稳定.
- HuR转位取决于p38 MAPK信号级联.
结论:
- 热冲击在转录后的水平上调节MKP-1基因表达.
- 通过p38 MAPK通路,HuR部分调解热冲击诱导的MKP-1mRNA稳定.
- 这突显了细胞应激反应中的新型调节机制.
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