描述和化学调制p62/SQSTM1/Sequestosome-1作为一个自N-识别因子
Su Jin Lee1, Hye Yeon Kim1, Min Ju Lee1
1Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, South Korea.
Methods in enzymology
|August 2, 2023
概括
蛋白质p62在自性Arg/N-degron路径中充当N-识别蛋白,将N-终端残留物与位载荷结合,以进行溶酶体降解. 模仿N-degron的小分子可以调节这个过程,以获得治疗效益.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 在Arg/N-degron途径的目标蛋白质通过ubiquitination和proteasomal途径降解.
- 自杀性Arg/N-degron通路利用p62受体来准荷载进行溶酶体降解.
- p62 (SQSTM1/Sequestosome-1) 作为一个N-识别素,结合N-终端残留物 (N-degrons).
研究的目的:
- 描述监测p62活动的方法,以其作为N-识别因子和自受体的双重作用.
- 探索小分子N-degron模仿的p62-依赖性宏自的调节.
- 了解神经退行和相关疾病的治疗潜力.
主要方法:
- 监测p62自聚合物,用于货物凝结.
- 评估p62与LC3在自膜上的相互作用,用于货物准.
- 评估p62-cargo复合物的降解由 lysosomal 水解酶.
主要成果:
- 结合p62与N端氨酸 (Nt-Arg) 诱导自我聚合和货物凝结.
- 通过LC3相互作用,p62促进了p62-cargo复合物的传递到自细胞体.
- lysosomal 水解酶会降解这些复杂物,清除细胞废物.
结论:
- p62在各种生物材料的自降解中发挥着关键作用,包括蛋白质聚合物和病原体.
- 小分子N-degron模仿剂提供了一个调节p62-依赖的宏自的策略.
- 这种途径调节对神经退行性和其他疾病具有治疗前景.
相关概念视频
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Delivery Pathways to the Lysosome
6.6K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.6K
Autophagy
4.3K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.3K
Export of Misfolded Proteins out of the ER
3.7K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.7K
Autophagic Cell Death
3.5K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.5K
Regulated Protein Degradation
7.4K
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...
7.4K


