在S161的RIPK1自酸化中介于细胞死亡和炎症
Lioba Koerner1,2, Xiaoming Li1,2, Eveline Silnov1,2
1Institute for Genetics, University of Cologne , Cologne, Germany.
The Journal of experimental medicine
|September 25, 2025
概括
在S161的受体相互作用蛋白激酶1 (RIPK1) 自酸化对RIPK1介导的细胞死亡和炎症至关重要. 这种酸化部位在调节炎症反应和细胞死亡途径方面发挥着关键作用.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 受体相互作用蛋白激酶1 (RIPK1) 是编程细胞死亡和炎症信号的关键调节者.
- 精确的RIPK1自化机制及其功能中的特定化位的作用仍然在很大程度上是未知的.
- RIPK1的失调与各种炎症性疾病有关.
研究的目的:
- 阐明RIPK1自化在特定部位的生理功能,特别是S161.1.
- 研究S161自化在RIPK1介导的细胞死亡和炎症中的作用.
- 了解不同RIPK1酸化位点之间的相互作用.
主要方法:
- 产生和利用具有特定RIPK1突变 (S161N,S166A,S161E) 的敲入小鼠模型.
- 评估RIPK1的催化活性和细胞死亡诱导 (亡,亡) 作为对突变的反应.
- 在RIPK1-介导细胞死亡条件下,在小鼠模型中评估皮肤炎症.
主要成果:
- 鉴定出S161自化对RIPK1介导的细胞死亡和炎症至关重要.
- S161N 替代部分损害了 RIPK1 催化活性和细胞死亡,但有效防止了皮肤炎症.
- 结合的S161N和S166A突变在预防RIPK1-介导的细胞死亡方面表现出协同作用,表明功能冗余.
- 相仿S161E突变证明足以诱导亡,甚至超过S166A突变的抑制作用.
结论:
- RIPK1 S161自酸化是RIPK1依赖细胞死亡和炎症反应的关键调节者.
- 在S161和S166化位点之间的功能相互作用控制RIPK1活动和下游信号.
- 针对RIPK1酸化,特别是S161,有可能在炎症性疾病中进行治疗干预.
更多相关视频
09:15Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells
Published on: October 20, 2022
2.7K
06:12Author Spotlight: THP-1 Macrophage Response to LPS/ATP — Unveiling the Pyroptosis, Apoptosis, and Necroptosis Spectrum
Published on: May 3, 2024
3.2K
相关概念视频
Autophagic Cell Death
4.3K
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...
4.3K
PI3K/mTOR/AKT Signaling Pathway
5.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.4K
The JAK-STAT Signaling Pathway
12.1K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
12.1K
The Extrinsic Apoptotic Pathway
8.1K
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...
8.1K
Overview of Cell Death
9.4K
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...
9.4K
Regulation of the Unfolded Protein Response
2.9K
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...
2.9K
