相关实验视频
Updated: Jul 23, 2025

10:36
Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
14.0K
压力传感器GCN2根据营养背景差异性控制结肠癌中的核糖体生物发生
Marie Piecyk1, Mouna Triki1, Pierre-Alexandre Laval1
1Centre de Recherche en Cancérologie de Lyon, INSERM U1052, CNRS 5286, Centre Léon Bérard, Université de Lyon, Université Claude Bernard Lyon 1, France.
Molecular oncology
|July 15, 2023
概括
一般控制的非降解性2 (GCN2) 激酶调节了核糖体的产生,影响了结肠癌细胞的存活和增殖. 向GCN2可以提高对结肠腺癌 (COAD) 的化疗有效性.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 营养素的可用性极大地影响瘤细胞的行为,稀缺性促进脱差和化学抵抗.
- 谷氨胺饥饿是一种特定的营养压力,影响癌细胞的命运.
- 核糖体生物生成可塑性与瘤细胞存活率和对治疗的反应有关.
研究的目的:
- 研究氨基酸传感器一般控制非降压2 (GCN2) 在代谢压力下调节核糖体生物发生的作用.
- 探索在结肠腺癌 (COAD) 中准GCN2途径的治疗潜力.
主要方法:
- 在代谢压力下对47S核糖体RNA (rRNA) 前体表达的分析.
- 评估GCN2阻塞对细胞死亡,细胞核应激和细胞亡的影响.
- 研究GCN2在富含营养条件中的作用及其对增殖的影响.
- 对mTORC1信号传递和自的GCN2-MetRS轴损伤的评估.
- 在COAD瘤中测试GCN2抑制和RNA聚合酶I (RNA聚I) 抑制剂的联合疗效.
主要成果:
- 在代谢压力下,GCN2抑制47SrRNA转录,而其阻断则诱导TP53介导的亡.
- 在营养丰富的条件下,GCN2通过刺激独立于综合应激反应 (ISR) 的47SrRNA转录来促进增殖.
- GCN2 损伤阻止了 metionyl-tRNA 合成酶 (MetRS) 的核转位,导致核应激,mTORC1 抑制和自.
- 在COAD模型中,抑制GCN2-MetRS轴显著增强了RNA pol I抑制剂的细胞毒性,包括氧沙.
结论:
- 根据营养背景,GCN2在控制核糖体生物发生方面发挥着差异性作用.
- GCN2-MetRS轴是细胞应激反应和COAD中的增殖的关键调节器.
- 药理上对GCN2和RNA polI的共同抑制为COAD治疗提供了一个有前途的治疗策略.
相关概念视频
Stringent Response in E. coli
31
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
31
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
The Nucleolus
8.9K
The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.9K
Regulation of the Unfolded Protein Response
2.5K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
Regulation of Expression at Multiple Steps
945
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
945
Translational Regulation
45
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
45

