描述WAC与R2TP和TTT伴侣复合物的相互作用,将葡萄糖和谷氨酸可用性与mTORC1活动联系起来
Sofía Cabezudo1, Natalia Cuervo1, Carmen García-Martín1
1Structural Biology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
FEBS open bio
|July 14, 2025
概括
WAC蛋白与mTOR和TELO2形成一个动态复合体,根据营养的可用性调节mTORC1的活动. 这种相互作用对于细胞对葡萄糖和谷氨胺水平的反应至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 分子机制的分子机制
- 蛋白相互作用 蛋白相互作用
背景情况:
- TELO2-TTI1-TTI2 (TTT) 和R2TP复合体是辅导体,有助于组装PIKK激酶,包括mTORC1.1.
- 华克蛋白是已知的mTORC1调节者,受营养可用性的影响,并与R2TP和TTT合作.
研究的目的:
- 定义WAC与R2TP和TTT的分子相互作用.
- 了解这些相互作用在不同营养条件下的mTORC1调节中的作用.
主要方法:
- 纯化蛋白相互作用试验.
- 在营养剥夺和再养下进行细胞复合分析.
- 转录和蛋白质组分析.
主要成果:
- WAC直接与mTOR-mLST8,R2TP和TELO2结合,但不与TTI1或TTI2结合.
- WAC与mTOR和TELO2形成动态复合体,在营养缺乏下强烈结合,在重新养时分离.
- 这些动态相互作用与mTORC1活动变化相关.
结论:
- WAC与mTOR和TELO2形成了一个受调节的复合体,有助于控制mTORC1对葡萄糖和谷氨酸的反应.
- 在人类癌症中,WAC,mTOR,R2TP和TT都被共同表达,这表明它们在癌症生物学中的作用.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
4.0K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.0K
mTOR Signaling and Cancer Progression
3.9K
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...
3.9K
Regulation of the Unfolded Protein Response
2.6K
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...
2.6K
Riboswitches
8.6K
Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
8.6K
Translational Regulation
104
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,...
104
Protein Folding Quality Check in the RER
3.8K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
3.8K


