Cuproptosis 的信号机制 激活 cGAS-STING 免疫通路
Chengyuan Zhu1, Jialiang Li1, Wanying Sun1
1State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China.
JACS Au
|November 1, 2024
概括
铜性诱导细胞死亡的cuproptosis通过释放线粒体DNA (mtDNA) 来激活先天免疫,以增强抗瘤T细胞反应. 这与可以抑制免疫力的亡形成鲜明对比,为癌症免疫疗法提供了新的途径.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 癌症治疗 癌症治疗
背景情况:
- 铜介导编程细胞死亡 (cuproptosis) 是一个有前途的抗瘤策略.
- 型亡包括脂酸蛋白聚合和线粒体应激,可能会影响免疫力.
- 了解cuproptosis免疫激活机制对于开发有效的癌症疗法至关重要.
研究的目的:
- 为了研究由cuproptosis和apoptosis激活的独特免疫信号通路.
- 探索铜复合体在调节癌症免疫反应中的作用.
- 确定将cuproptosis与先天性和适应性抗瘤免疫联系起来的分子机制.
主要方法:
- 新型非标记光分子工具 (Cu-DPPZ-Py+和Cu-DPPZ-Ph) 的合成.
- 利用这些工具研究由cuproptosis和apoptosis诱导的差异性免疫信号.
- 研究线粒体DNA (mtDNA) 释放和cGAS-STING通路的激活.
主要成果:
- 由Cu-DPPZ-Py+和Cu-Elesclomol诱导的cuproptosis触发了显著的mtDNA释放.
- 这种mtDNA释放激活cGAS-STING天生的免疫通路,增强T细胞抗瘤免疫力.
- 由Cu-DPPZ-Ph诱导的亡导致caspase-3的释放和相关的免疫抑制.
结论:
- 质亡有效地将线粒体压力与cGAS-STING免疫通路联系起来,促进抗瘤免疫力.
- 这项研究阐明了 cuproptosis 和 apoptosis 的不同免疫调节作用.
- 这些发现支持开发基于cuproptosis的新型癌症免疫疗法策略.
相关概念视频
02:33Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
01:22Amplifying Signals via Enzymatic Cascade
8.3K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.3K
01:17The Extrinsic Apoptotic Pathway
6.3K
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...
6.3K
01:20The JAK-STAT Signaling Pathway
8.7K
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...
8.7K
01:16Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
01:22Activation and Inactivation of G Proteins
6.8K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
6.8K