相关实验视频
Updated: Jul 18, 2025

09:16
Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
8.5K
一个KEAP1传感器素的化促进NRF2激活
Lara Ibrahim1, Caroline Stanton1, Kayla Nutsch2
1Department of Molecular Medicine, Scripps Research, San Diego, CA 92037, USA; Department of Chemistry, Scripps Research, San Diego, CA 92037, USA.
Cell chemical biology
|August 24, 2023
概括
细胞平衡依赖于新陈代谢和压力反应之间的通信. 新的研究表明,酸无水化物可以通过修改KEAP1蛋白来激活NRF2应激反应途径.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 分子信号传输的方法
背景情况:
- 细胞平衡取决于代谢途径和应激反应信号之间的相互作用.
- 反应性代谢物可以通过共价蛋白修饰来调节应激反应性转录因子,如NRF2.
- 该NRF2抑制剂KEAP1含有由各种代谢物修改的传感器囊蛋白,激活NRF2的细胞保护程序.
研究的目的:
- 确定连接中央碳代谢与NRF2激活的新型调节节点.
- 为了研究酸盐无水化物在NRF2信号传递中的作用.
主要方法:
- 利用基于shRNA的屏幕向中央碳代谢中的酶.
- 研究了 succinyl-CoA合成酶的遗传枯竭和直接使用 succinic anhydride的影响.
- 分析了KEAP1在lysine 131.1中的N-化.
主要成果:
- 顺无水化物,通过顺-CoA合成酶耗尽或直接服用而升高,激活NRF2信号传递.
- 酸无水化物在KEAP1上诱导了lysine 131的N-succinylation. 在KEAP1上诱导了酸无水化物.
- KEAP1可以通过氨酸和氨酸残留物感知反应性代谢物.
结论:
- KEAP1作为传感器,对比以前所知的更广泛的反应性代谢信使进行传感.
- 这项研究扩大了对新陈代谢如何调节应激反应信号通路的理解.
- 通过氨酸无水化物对KEAP1的氨酸修饰识别了NRF2激活的新机制.
相关概念视频
NF-κB-dependent Signaling Pathway
7.5K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.5K
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
Covalently Linked Protein Regulators
6.9K
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....
6.9K
Regulation of the Unfolded Protein Response
2.5K
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...
2.5K
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Protein Modifications in the RER
5.3K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.3K

