阿里尔碳化合物受体 (AHR) 通过对抗TOX表达抑制了 (As3+) 诱导的恶性转变
Wenxuan Zhang1, Ziwei Wang1, Yao Fu1
1Stony Brook Cancer Center, Department of Pathology, Renaissance School of Medicine, Stony Brook University. Lauterbur Drive, Stony Brook, NY 11794, USA.
International journal of biological sciences
|April 30, 2025
概括
环境中的暴露会导致癌症. 这项研究表明,烯碳化合物受体 (AHR) 通过抑制致癌性TOX蛋白抑制癌症干细胞的形成,揭示了致癌的新机制.
科学领域:
- 环境毒理学环境毒理学
- 癌症生物学 癌症生物学
- 癌症发生的分子机制.
背景情况:
- 由于其致癌潜力,环境中的暴露是严重的公共卫生问题.
- 阿里碳水化合物受体 (AHR) 抑制与诱导的致癌症有关,但其在恶性转变和癌症干细胞 (CSC) 形成中的确切作用尚不清楚.
研究的目的:
- 调查AHR在诱导的CSC发育中的作用,并阐明潜在的分子机制.
- 检查AHR如何影响CSCs的形成,以应对低剂量暴露.
主要方法:
- 在BEAS-2B细胞中利用了CRISPR-Cas9基因编辑.
- 进行了RNA测序和免疫沉试验.
- 分析了TOX交互原子,并进行了丰富分析.
主要成果:
- 亚利碳化合物受体 (AHR) 通过TOX的转录抑制抑制低剂量 (0.5μM) 诱导的CSC形成.
- 托克斯倒置抑制了CSC的形成,而托克斯过度表达增强了cMYC,一种与CSC相关的转录因子.
- 托克斯相互作用组分析揭示了与可能调节托克斯稳定性和活性的蛋白质的关联,这与癌症途径有关.
结论:
- 亚利碳化合物受体 (AHR) 通过抑制致癌因子TOX的作用,在诱导的致癌过程中起到瘤抑制作用.
- 托克斯促进CSC的形成,并与非免疫癌症相关.
- 这项研究为诱导的致癌机制提供了新的见解,突出了AHR-TOX途径.
相关概念视频
01:31Transducer Mechanism: Nuclear Receptors
1.2K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.2K
01:26Anticholinesterase Agents: Poisoning and Treatment
733
Anticholinesterases, also known as cholinesterase inhibitors, work by blocking the breakdown of acetylcholine, leading to its accumulation in the synaptic cleft. This accumulation indirectly enhances both muscarinic and nicotinic actions. These agents are classified as reversible or irreversible based on their mechanism of action.
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
Irreversible agents form a strong bond with the cholinesterase enzyme, making it inactive. The breakdown of the phosphorylated enzyme is...
733
01:19Allosteric Proteins-ATCase
5.6K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.6K
01:28Acid Suppressive Drugs for Peptic Ulcer Disease: Histamine H2-Receptor Antagonists
365
Histamine H2 receptors, which are intricately located on the basolateral membrane of parietal cells, play a crucial role in modulating gastric acid secretion. When released from enterochromaffin-like cells, histamine engages H2 receptors, initiating the cyclic AMP (cAMP) pathway. In this pathway, adenylyl cyclase converts ATP into cAMP, elevating intracellular cAMP levels. The activation of protein kinase A follows, stimulating the proton pump. This stimulation prompts the secretion of hydrogen...
365
01:26Physical Properties of Amines
2.9K
Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
2.9K
01:18Indirect-Acting Cholinergic Agonists: Mechanism of Action
1.5K
Indirect-acting cholinergic agonists work by interacting with an enzyme called acetylcholinesterase (AChE) in the synaptic cleft. They can be reversible or irreversible inhibitors and have different effects on the enzyme.
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
1.5K