在死细胞细胞死亡中,蛋白质的形状变化向细胞死亡发出信号
Hanadi Hoblos1, Wayne Cawthorne1, André L Samson1
1Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Parkville, VIC 3052, Australia.
Trends in biochemical sciences
|December 27, 2024
概括
死细胞灭绝,一个被编程的细胞死亡途径,由蛋白质组装和修饰来调节. 准这些关键的效应蛋白为炎症性疾病提供了新的治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 亡是一种被编程的细胞死亡途径,对先天免疫非常重要.
- 死体亡的失调与各种炎症性疾病有关.
- 关键的作用者包括Z-DNA结合蛋白-1 (ZBP1),RIPK1,RIPK3和MLKL.
研究的目的:
- 探索如何调节蛋白质构成和亡因子的组装.
- 为了研究翻译后修改和分子间相互作用在亡中的作用.
- 为了识别在亡途径内的潜在的治疗点.
主要方法:
- 对ZBP1,RIPK1,RIPK3和MLKL的蛋白质构造和更高阶组合的分析.
- 研究翻译后的修改 (酸化,无处不在,脂化).
- 检查影响尸体信号流的分子间相互作用.
主要成果:
- 蛋白质构成和亡因子的组装是动态调节的.
- 翻译后的修改和分子间相互作用微调死细胞信号传递.
- 阐明了控制亡途径活性的特定分子机制.
结论:
- 调节关键亡因子的蛋白质构成是一种有前途的治疗策略.
- 向死的途径组件为治疗炎症性疾病提供了潜在的潜力.
- 进步对细胞死亡信号的分子理解,开辟了新的药物开发途径.
相关概念视频
Overview of Cell Death
7.0K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.0K
Necrosis
4.3K
Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become...
4.3K
The Extrinsic Apoptotic Pathway
6.2K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.2K
The Intrinsic Apoptotic Pathway
6.4K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.4K
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
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


