氧尿素调节酵母体内皮质网膜中的硫化-硫化稳态
Yuki Takano1, Yuki Ishiwata-Kimata2, Ryo Ushioda3,4
1Graduate School of Science, Nagoya City University, Nagoya, Japan.
Life science alliance
|June 20, 2025
概括
基尿素 (HU) 选择性地抑制酵母体内光蛋白的内细胞网关联降解 (ERAD),独立于细胞循环停止. 这一发现揭示了HUHU.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 氧尿素 (HU) 是一种广泛使用的实验室剂,用于诱导S相停止和临床化疗.
- 其精确的药理学,副作用和对器官稳定性的影响仍然不完全理解.
- 细胞内膜网关联降解 (ERAD) 对于维持ER内的蛋白质稳定至关重要.
研究的目的:
- 研究氧尿素 (HU) 对内质网膜 (ER) 内的蛋白质降解途径的特定影响.
- 阐明HU影响ERAD,特别是ERAD-L路径的机制.
- 探索HU在细胞氧化还原平衡中的作用.
主要方法:
- 使用了芽酵母 (Saccharomyces cerevisiae) 的模型.
- 使用特定的测试来监测错误折叠的光线,膜和细胞质蛋白质的降解.
- 评估了HU对S相停止和ERAD-L通路活性的影响.
- 在Ero1缺乏细胞中检查了HU在减轻减小压力的作用.
主要成果:
- 氧尿素 (HU) 选择性地抑制了酵母体中与ER相关的光线错折叠蛋白质 (ERAD-L通路) 的降解.
- 这种抑制是独立于HU对S相停止的已知影响.
- HU没有影响错误折叠的ER膜蛋白或细胞质蛋白的降解.
- HU的作用与减少光基板中的二硫化物键有关,从而促进它们的降解.
- 在缺乏Ero1的细胞中,HU减轻了减少性压力表型,Ero1是氧化蛋白折叠的必要酶.
结论:
- 基尿素 (HU) 特别向并抑制ERAD-L通路,影响光线错误折叠蛋白质的降解.
- 该机制涉及调节ER光线内的硫化-硫化稳态.
- 这些发现表明,超出其已知对DNA复制和细胞循环进展的影响,HU的新型作用超出了其已知的影响,影响ER蛋白质稳定和氧化还原平衡.
更多相关视频
10:57Growth-based Determination and Biochemical Confirmation of Genetic Requirements for Protein Degradation in Saccharomyces cerevisiae
Published on: February 16, 2015
9.9K
07:16Resin-Assisted Capture Coupled with Isobaric Tandem Mass Tag Labeling for Multiplexed Quantification of Protein Thiol Oxidation
Published on: June 21, 2021
1.9K
相关概念视频
Protein Modifications in the RER
5.6K
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...
5.6K
Sulfur Assimilation
80
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
80
Export of Misfolded Proteins out of the ER
3.9K
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...
3.9K
Preparation and Reactions of Thiols
6.7K
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
6.7K
