BRCC36 脱基酸 HMGCR 调节铁和热之间的相互作用
Haiyan Wang1,2,3, Long Shu1,3, Cairui Lv1,3
1Key Laboratory of Carcinogenesis and Cancer Invasion (Central South University, Ministry of Education), Department of Pathology, Xiangya Hospital, Central South University, Hunan, 410078, China.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
|January 5, 2024
概括
铁和热有通过HMGCR调解的对抗关系. BRCC36通过抑制铁亡和促进铁亡促进肝细胞癌 (HCC),提供治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 编程的细胞死亡
背景情况:
- 编程细胞死亡 (PCD) 包含各种形式,如亡,自和铁亡,它们之间有潜在的相互作用.
- 铁和热,两个不同的PCD途径之间的关系,仍然在很大程度上未被探索.
- 肝细胞癌 (HCC) 是一个主要的全球健康问题,需要新的治疗策略.
研究的目的:
- 为了研究铁和热之间潜在的相互作用.
- 阐明3 - - 3 - 甲基 - - 同酶A减少酶 (HMGCR) 在铁和热之间的相互作用中的作用.
- 通过检查BRCC36.6的功能来确定肝细胞癌 (HCC) 的新型治疗点.
主要方法:
- 在铁和热条件下对HMGCR的细胞局部化研究.
- 研究BRCC36在HMGCR上的脱活动.
- 评估BRCC36在HCC扩散,迁移,入侵和瘤生长中的作用.
- 在HCC模型中评估BRCC36抑制剂蒂奥鲁丁.
主要成果:
- 铁和热之间的相互对抗关系被揭示出来,HMGCR作为一个关键的调解者.
- 在Pyroptosis诱导后,HMGCR的局部化从线粒体转移到内 плазма网膜.
- BRCC36二基化HMGCR,抑制铁亡和促进热亡,从而推动HCC的进展.
- 提奥鲁丁的BRCC36抑制抑制了HCC的生长.
结论:
- 这项研究揭示了HMGCR和BRCC36.6调节的铁和热之间的新型对抗性交叉声.
- 在HCC中,BRCC36作为瘤基因起作用,促进瘤生长和进展.
- 向BRCC36为HCC治疗提供了一个有前途的治疗策略,为诊断和治疗提供了新的途径.
相关概念视频
Export of Misfolded Proteins out of the ER
3.6K
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...
3.6K
The Unfolded Protein Response
4.6K
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...
4.6K
Regulated Protein Degradation
7.3K
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...
7.3K
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
Covalently Linked Protein Regulators
6.8K
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....
6.8K
Receptor Downregulation in MVBs
2.1K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.1K


