USP13二基因化 p62/SQSTM1 诱导自和 Nrf2 释放以激活抗氧化剂反应基因
相关实验视频
Updated: Jul 15, 2025

08:26
Monitoring Stub1-Mediated Pexophagy
Published on: May 12, 2023
1.6K
Bin Lee1, Young Hun Kim2, Woori Lee3
1Department of Microbiology, Yonsei University College of Medicine, Seoul, South Korea; Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Free radical biology & medicine
|September 30, 2023
概括
乌比奎丁特异性蛋白酶13 (USP13) 将序列组1 (p62) 进行二基因化,增强其稳定性并促进自. 这一发现确定了USP13作为一种潜在的治疗目标,用于与自有关的疾病.
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 生物化学
背景情况:
- SQSTM1/p62是一种关键的支架蛋白,调节选择性自和信号通路,如mTORC1和Keap1-Nrf2.
- 翻译后的修改,包括ubiquitination,控制p62的功能,但它的 deubiquitination机制在很大程度上是未知的.
研究的目的:
- 调查SQSTM1/p62的二维基因化,并确定负责的酶.
- 阐明p62双化对细胞过程和疾病通路的功能后果.
主要方法:
- 同免疫沉试验确定USP13与p62.6结合.
- 实验室二基化试验证实USP13对p62.2.的酶活性.
- 西方涂抹和自流量测试以评估p62稳定性,寡合化和自降解.
主要成果:
- 乌比基因特异蛋白酶13 (USP13) 直接与SQSTM1/p62结合,并在PB1域的Lys7 (K7) 中去除乌比基因.
- 通过USP13介导的二维基化增加了p62蛋白的稳定性,并促进了其寡合化.
- 这一过程增强了自,导致Keap1的降解,从而促进了Nrf2介导的抗氧化反应.
结论:
- USP13在通过duebiquitination调节p62的稳定性和功能方面发挥着至关重要的作用.
- 通过USP13调节p62影响自和Keap1-Nrf2抗氧化途径.
- USP13代表了管理与自有关的疾病的潜在治疗标.
相关概念视频
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
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
Abnormal Proliferation
4.6K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.6K
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
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
Autophagic Cell Death
3.4K
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...
3.4K

