在芽酵母中,TOR2在拉帕素诱导的寿命延长中发挥着核心作用
Dongseong Seo1, Gulperi Yalcin1, Hyeonjun Jang1
1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02481, Republic of Korea.
Biochemical and biophysical research communications
|September 6, 2024
概括
而TOR2基因,而不是TOR1,可以调解拉巴胺.
科学领域:
- 分子生物学分子生物学
- 衰老研究研究 衰老研究
- 细胞信号传递 细胞信号传递
背景情况:
- 拉帕素 (TOR) 蛋白的标对细胞信号传递至关重要,并且在物种之间高度保存.
- 拉巴胺可以延长寿命,但其精确的TOR介导机制尚未完全理解.
- 发芽的酵母Saccharomyces cerevisiae有两个TOR类基因,TOR1和TOR2,与哺乳动物的单一TOR基因不同.
研究的目的:
- 调查TOR1和TOR2在调解拉巴素延长寿命的作用中的特定作用.
- 为了确定酵母中的哪个TOR对应物是拉帕米抗衰老作用的主要目标.
主要方法:
- 在Tor2p的FRB域中设计了一个特定的点突变 (Ser-1975-Ile),以抑制拉巴胺素结合.
- 鉴于TOR1基因状态,评估了这种突变对拉帕米辛在酵母菌中延长寿命的影响.
主要成果:
- 在Tor2p中发生的工程突变取消了通常在拉帕治疗中观察到的寿命延长.
- 这种效应独立于TOR1基因的存在或不存在.
- 这些发现强烈地表明TOR2是拉帕米辛对寿命影响的关键调解者.
结论:
- 鉴定出TOR2基因是拉帕米延长寿命的主要媒介.
- TOR2很可能是功能性哺乳动物 ортолог,参与了拉帕米的抗衰老作用.
- 这项研究为开发针对TOR复合体的新型抗衰老疗法铺平了道路.
相关概念视频
03:03mTOR 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
01:22PI3K/mTOR/AKT Signaling Pathway
3.4K
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...
3.4K
02:41Telomeres and Telomerase
23.2K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
23.2K
01:28Yeast Signaling
14.5K
Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
14.5K
01:29Replication in Eukaryotes
13.6K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.6K
01:31Regulation of the Unfolded Protein Response
2.4K
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...
2.4K