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TFE3异形对细胞移动性和侵入性的差异性贡献
Pablo S Contreras1, José A Martina1, Katie Rollins1
1Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
两个转录因子TFE3异型,TFE3-L和TFE3-S,来自不同的启动位点. TFE3-L促进细胞迁移和入侵,可能与压力下转移相关.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 转录因子TFE3调节细胞对压力的反应,维持平衡和生存.
- 替代转录启动部位产生不同的TFE3蛋白质异型.
研究的目的:
- 为了研究两个TFE3异型,TFE3-L和TFE3-S之间的功能差异.
- 为了确定TFE3异型在移徙和入侵等细胞过程中的作用.
主要方法:
- 通过替代转录启动生成TFE3异形的分析.
- 评估TFE3异形稳定性和由氧降解和mTORC1.1.的调节.
- 基因表达,细胞迁移和入侵试验中的TFE3-L和TFE3-S功能的比较.
- 在结核性硬化细胞模型中,TFE3-L的耗尽.
主要成果:
- 产生了两个TFE3异型,TFE3-L和TFE3-S;TFE3-L是由于光降解而具有应激诱导性,而TFE3-S是构成性表达的.
- 这两种异构体都受到Rags/mTORC1的调节,并类似地诱导 lysosomal/autophagic 基因.
- 与TFE3-S相比,TFE3-L显著增强了细胞迁移和入侵.
- 在状硬化模型中,TFE3-L 枯竭降低了运动性和侵入性.
结论:
- TFE3异型体表现出部分功能冗余,但在细胞移动性中发挥着不同的作用.
- 压力诱导的TFE3-L积累可能与转移性行为有关.
- 了解 TFE3 异形函数,可以了解细胞应激反应和癌症进展.
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