向出口因-1的染色质结合会破坏NFAT和T细胞激活
Yi Fan Chen1,2, Maryam Ghazala1,2, Ryan M Friedrich1,2
1Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Nature chemical biology
|March 26, 2024
概括
输出素-1 (XPO1) 通过与染色素结合,对T细胞激活至关重要. 新的XPO1调节器准了这一功能,提供了超越癌症的治疗潜力,包括针对自身免疫性疾病.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 输出蛋白-1 (XPO1/CRM1) 中介于核输出,并在细胞分裂中发挥作用.
- 像Selinexor这样的XPO1抑制剂被FDA批准用于癌症治疗.
- XPO1在T细胞激活中的确切作用尚不清楚.
研究的目的:
- 研究XPO1在T细胞激活中的作用.
- 识别具有独特作用机制的新型XPO1调节器.
主要方法:
- 染色体免疫沉测定用于评估XPO1结合.
- T细胞激活检测.T细胞激活检测.
- 新型小分子抑制剂的开发和测试.
主要成果:
- XPO1表现出细胞类型依赖的染色质结合功能,这对于T细胞激活至关重要.
- 对于NFAT转录因子占用,需要XPO1染色体结合.
- 确定了一种新的XPO1调节器类别,可以破坏XPO1染色体结合,而不会影响核出口或引起细胞毒性.
结论:
- XPO1在通过染色体结合来调节T细胞激活方面发挥着重要作用.
- 新型XPO1调节器为T细胞驱动的自身免疫性疾病提供了一种治疗策略,与当前的瘤治疗不同.
更多相关视频
13:20Chromatin Immunoprecipitation ChIP to Assay Dynamic Histone Modification in Activated Gene Expression in Human Cells
Published on: July 29, 2010
28.7K
10:57NF-κB-dependent Luciferase Activation and Quantification of Gene Expression in Salmonella Infected Tissue Culture Cells
Published on: January 12, 2020
10.6K
相关概念视频
NF-κB-dependent Signaling Pathway
7.4K
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Nuclear Export
3.6K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
Co-activators and Co-repressors
7.3K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.3K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Directionality of Nuclear Transport
3.2K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.2K
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
