哺乳动物TOR:一个恒温的ATP传感器
P B Dennis1, A Jaeschke, M Saitoh
1The Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
概括
拉帕米辛是一种抗癌药物,向固体瘤. 研究人员发现,哺乳动物的目标拉巴胺素 (mTOR) 途径感知细胞能量水平 (ATP),而不仅仅是氨基酸,影响癌症生长.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 拉帕米是一种有效的抗癌药物,用于固体瘤.
- 固体瘤的生长,特别是在缺氧的情况下,依赖于营养和基因的供应.
- 猛素的哺乳动物标 (mTOR) 调节核糖体生物发生和细胞生长,以响应营养的可用性,特别是氨基酸.
研究的目的:
- 研究mTOR路径的调节机制,以应对营养度的变化.
- 为了确定mTOR通路的调节是否受到细胞内ATP水平的影响,而不依赖于氨基酸丰度.
- 为了确定mTOR作为细胞ATP度的直接传感器.
主要方法:
- 研究了细胞内ATP度对mTOR通路的影响.
- 研究了氨基酸丰度在mTOR通路调节中的作用.
- 评估了mTOR对ATP的直接传感能力.
主要成果:
- mTOR通路的活性是由细胞内ATP度调节的.
- 这种依赖ATP的调节独立于氨基酸水平发生.
- mTOR作为细胞内ATP的直接传感器.
结论:
- 哺乳动物的拉巴胺素目标 (mTOR) 途径对细胞能量状态 (ATP) 很敏感.
- mTOR充当ATP传感器,将能量信号整合到生长调节中.
- 这一发现为癌症代谢和针对mTOR的治疗策略提供了新的见解.
相关概念视频
ATP Driven Pumps I: An Overview
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and are...
Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
mTOR Signaling and Cancer Progression
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...
ATP Driven Pumps II: P-type Pumps
The P-type pumps are a large family of integral membrane transporter ATPases. They are divided into five major types based on substrate specificity, from I to V.
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
A typical P-type pump has three cytosolic domains: nucleotide-binding (N), phosphorylation (P), and activator (A) domains. These domains are connected to the membrane-spanning helices by short amino acid segments. ATP hydrolysis and covalent phosphoenzyme intermediate formation are crucial parts of the catalytic cycle. At the highly...
ATP Driven Pumps III: V-type Pumps
V-type pumps are ATP-driven pumps found in the vacuolar membranes of plants, yeast, endosomal and lysosomal membranes of animal cells, plasma membranes of a few specialized eukaryotic cells, and some prokaryotes. They are also known as the V1Vo-ATPase, that couple ATP hydrolysis to transport protons against a concentration gradient.
The peripheral or cytosolic V1 domain with eight subunits is involved in ATP hydrolysis. The integral or transmembrane V0 domain containing at least five subunits...
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PI3K/mTOR/AKT Signaling Pathway
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 rapamycin-insensitive companion...


