一个保存的无处不在的途径决定了长寿,以应对饮食限制
Andrea C Carrano1, Zheng Liu, Andrew Dillin
1Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Nature
|June 26, 2009
概括
饮食限制可以通过C. elegans中的HECT E3泛酸酶WWP-1和UBC-18酶延长寿命. 在WWP-1中使用WWP-1.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 衰老研究研究 衰老研究
背景情况:
- 饮食限制 (DR) 是一种保护性干预,可以在各种物种中延长寿命.
- 这表明了涉及营养感知和生存途径的潜在保存机制.
- 了解这些途径对于制定促进健康衰老的策略至关重要.
研究的目的:
- 调查HECT E3泛素酶WWP-1在调节饮食限制后寿命中的作用.
- 为了确定下游因素和WWP-1中介寿命的酶要求.
- 阐明WWP-1对DR诱导的寿命延长的具体贡献.
主要方法:
- 使用了模型生物Caenorhabditis elegans.
- 操纵了wwp-1 (野生型和催化死突变) 和ubc-18.c的表达.
- 在自由食和饮食限制条件下的估计寿命.
- 研究的遗传依赖性包括pha-4和daf-16.
主要成果:
- 在C. elegans.中,wwp-1的过度表达延长了长达20%的寿命.
- WWP-1的长寿促进作用依赖FOXA转录因子pha-4,但不是DAF-16.
- 丧失wwp-1功能抑制了DR诱导的寿命,而其催化活性是必不可少的.
- 发现E2无素结合酶UBC-18对于DR诱导的寿命至关重要和特异,与WWP-1相互作用.
结论:
- 在C. elegans中,WWP-1作为对饮食限制的反应,作为寿命的积极调节者.
- 与UBC-18结合,WWP-1的基因酶活性对于DR介导的寿命至关重要.
- 这些发现揭示了一种涉及WWP-1和UBC-18的全新的全域化酶通路,该通路在营养有限的条件下调节寿命.
相关概念视频
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Regulated Protein Degradation
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Regulation of the Unfolded Protein Response
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...

