在T细胞中拼接的共价向向
Kevin A Scott1, Hiroyuki Kojima1, Nathalie Ropek1
1Department of Chemical Immunology and Proteomics, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
Cell chemical biology
|November 26, 2024
概括
研究人员开发了针对剪接因子SF3B1的化学探针,导致ITK的选择性T细胞损失. 这项工作突出了免疫状态依赖的蛋白质表达变化和拼接因子的共价向潜力.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 对RNA拼接的治疗向具有显著的兴趣,但用于拼接蛋白质的化学探针是有限的.
- 介素二诱导性T细胞激酶 (ITK) 在T细胞信号传递中起着至关重要的作用.
研究的目的:
- 开发化学探测器以准拼接因子.
- 研究T细胞中依赖状态的蛋白质损失的机制.
- 探索共价化学的潜力,以准拼接因子.
主要方法:
- 立体同位素烯胺EV96和类似物的合成和应用.
- 涉及蛋白质周转率和替代拼接分析的机制研究.
- 基于活动的蛋白质分析 (ABPP) 使用电友侦察碎片.
主要成果:
- EV96通过向SF3B1.1. 选择性诱导T细胞状态依赖的ITK损失.
- 国家依赖与差异性蛋白质周转率和ITK mRNA替代拼接有关.
- 在T细胞中证明了众多拼接因子和调节者的共价结合性.
结论:
- 拼接的化学干扰可以诱导蛋白质表达的免疫状态依赖的变化.
- 聚合因子的共价向是一种有前途的治疗策略.
相关概念视频
RNA Splicing
56.0K
Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.0K
Pre-mRNA Processing: RNA Splicing
5.2K
5.2K
Alternative RNA Splicing
21.0K
Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.0K
Cytotoxic T Cells-mediated Immune Response
849
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
849
T Cell Activation and Clonal Selection
669
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
669
Chromatin Structure and RNA Splicing
2.7K
2.7K


