血清错误翻译通过P茎诱导了通过P茎的综合应激反应
1Department of Cell Biology and Molecular Genetics, The University of Maryland, College Park, Maryland, USA.
The Journal of biological chemistry
|March 27, 2025
概括
氨基酸-tRNA合成酶 (aaRS) 错误导致Ser错误整合,激活综合应激反应 (ISR). 这种激活涉及核糖体停滞,而不是未充电的tRNA,影响细胞健康和疾病.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 氨基酸-tRNA合成酶 (aaRSs) 对于精确的蛋白质合成至关重要.
- aaRSs中的突变与人类疾病有关,包括神经系统疾病和癌症.
- 氨基化错误对细胞应激反应的影响尚不清楚.
研究的目的:
- 研究氨基化错误如何影响真核细胞中综合应激反应 (ISR).
- 阐明特定氨基酸错误结合引发ISR的机制.
- 确定tRNA水平和核糖体动态在ISR激活中的作用.
主要方法:
- 利用基于细胞的测试来监测ISR激活.
- 研究了特定的氨基酸-tRNA合成酶缺陷和tRNA突变的影响.
- 分析了核糖体组件,特别是P茎,在应激反应途径中的参与.
主要成果:
- 氨酸被错误地纳入氨酸和氨酸编码子会激活ISR.
- 通过血清错误翻译激活ISR是独立于未加电的tRNA积累.
- 对于ISR激活,需要带蛋白质组P茎关联,这表明带蛋白质组停滞和碰撞.
结论:
- 某些氨基化错误,如血清酸错误结合,可以长期激活ISR.
- 这些发现表明,核糖体停滞是ISR激活的关键机制.
- 这项研究提供了关于蛋白质合成错误如何导致细胞压力和疾病进展的见解.
相关概念视频
Regulation 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
The Unfolded Protein Response
4.5K
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...
4.5K
Directing Proteins to the Rough Endoplasmic Reticulum
7.2K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.2K
Post-translational Translocation of Proteins to the RER
5.6K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
5.6K
Cotranslational Protein Translocation
7.2K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.2K
Insertion of Single-pass Transmembrane Proteins in the RER
6.6K
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
6.6K


