一种设计型聚Q融合蛋白通过将P65/RelA隔离到聚合物中来调节NF-κB信号传输
Xiang-Le Zhang1,2,3, Lei-Lei Jiang1, Heng-Tong Duan1,3
1Key Laboratory of RNA Innovation, Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, 200031, People's Republic of China.
Scientific reports
|July 27, 2025
概括
研究人员开发了一种新型的融合蛋白来向和隔离P65,这是NF-κB通路的关键组成部分. 这种方法有效地减少了促炎性细胞因子的产生,为炎症和自身免疫性疾病提供了潜在的治疗策略.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 药物发现 药物发现 药物发现
背景情况:
- 激活B细胞 (NF-κB) 信号通路的核因子卡帕-光链增强剂调节促炎细胞因子表达和先天免疫力.
- 失调的NF-κB激活与慢性炎症和自身免疫性疾病有关.
- 聚氨酸 (polyQ) 融合策略可以隔离标蛋白来调节生物过程.
研究的目的:
- 开发一种设计型多Q融合蛋白 (Atx793Q-N172-LDEL) 以专门隔离NF-κB的P65亚单元.
- 研究P65封存对NF-κB信号活动和下游基因表达的影响.
- 评估针对炎症性疾病的P65的治疗潜力.
主要方法:
- 构建了一个设计型多Q融合蛋白,Atx793Q-N172-LDEL,结合一个LDEL用于P65相互作用.
- 利用融合蛋白诱导细胞P65.5的聚合和封存.
- 评估了P65绑定对其核转位,NF-κB信号活动和下游基因表达 (例如TNF-α,IL-6) 的影响.
主要成果:
- 该Atx793Q-N172-LDEL融合蛋白与细胞P65成功相互作用并将其隔离成聚合物.
- 封存P65阻碍了其核转移,并减少了其核丰度.
- NF-κB信号活动和下游炎症基因的表达,包括TNF-α和IL-6,显著减弱.
结论:
- 设计者polyQ融合蛋白通过准P65.5,有效调节NF-κB信号传递.
- 这种P65封存策略证明了治疗炎症和自身免疫性疾病的治疗潜力.
- 直接准P65为开发炎症病的治疗方法提供了一种新的方法.
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