希尔普斯 (HILPS) 是一种长非编码RNA,对于人类的全球氧气传感至关重要
Zhi Chen1,2, Chan Chen1,2, Lei Xiao3
1Department of Urology, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.
Science advances
|November 22, 2023
概括
一种新的长非编码RNA,HILPS,稳定了PLK1,增强了HIF1α活性,用于细胞适应低氧. 在正常和癌细胞中,HILPS枯竭会导致低氧适应的严重缺陷.
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:
- 细胞适应低氧 (低氧) 对于甲基动物的生存至关重要.
- 氧气感应的机制在物种之间有所不同,仍然不完全理解.
- 缺氧诱导因子1α (HIF1α) 是细胞对缺氧反应的关键调节者.
研究的目的:
- 为了功能性地表征一种参与低氧适应的新型长非编码RNA (lncRNA).
- 阐明这个lncRNA在HIF1α调节途径中的作用.
- 为了确定氧气传感机器的新组件.
主要方法:
- 鉴定和命名一个新的lncRNA,HILPS (低氧诱导的lncRNA用于PLK1稳定).
- 在正常和癌细胞中HILPS表达的分析在normoxia和hypoxia下.
- 研究HILPS,波罗样酶1 (PLK1) 和HIF1α之间的相互作用.
- 在低氧期间HILPS耗尽后对细胞适应缺陷的评估.
主要成果:
- 希尔普斯被HIF1α强烈诱导,并与PLK1结合,防止其蛋白质体降解.
- 稳定PLK1酸化HIF1α,增强其稳定性,并创建一个积极的前循环.
- 在正常和癌细胞中,HILPS的耗尽导致缺氧适应的灾难性缺陷.
- HILPS-PLK1-HIF1α通路形成了一个关键的氧气传感轴.
结论:
- 涉及HILPS,PLK1和HIF1α的新型调节途径被确定为氧气传感的关键机制.
- 这一途径对于包括癌细胞在内的人体细胞的细胞适应低氧是必不可少的.
- HILPS-PLK1-HIF1α轴代表了理解人类对缺氧的生理和病原反应的重大发现.
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