概括
葡萄糖皮质激素激素通过DNA结合激活基因表达. 这项研究表明,葡萄糖皮质体受体仅在激素治疗后与DNA结合部位相互作用,而不是之前.
科学领域:
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
- 遗传学 是一个遗传学.
背景情况:
- 葡萄糖皮质激素通过受体结合到特定的DNA序列 (葡萄糖皮质反应元素,GREs) 来调节基因表达.
- 一个普遍的模型表明,细胞质受体在激素结合后转移到细胞核,从而增加DNA亲和力.
- 最近的研究表明,即使没有连接体,其他类固醇受体也是核的,这促使人们对葡萄糖皮质体受体行为的调查.
研究的目的:
- 在激素结合之前,研究自由葡萄糖皮质体受体是否与其DNA结合部位在体内相互作用.
- 检查激素结合在葡萄糖皮质体受体与GREs的体内相互作用中的作用.
主要方法:
- 基因组足迹技术被用于检测体内蛋白质-DNA相互作用.
- 用二甲基硫酸盐的反应性来评估受体-DNA结合的变化.
- 在肝瘤细胞 (表达氨酸转移酶基因,TAT) 和纤维细胞 (不表达TAT) 中进行了实验.
- 此外,还使用克隆DNA和部分净化的受体进行了体外测试.
主要成果:
- 在TAT基因的GREs内体内蛋白质-DNA相互作用的变化仅在肝瘤细胞中进行激素治疗后被检测出来.
- 在纤维细胞中没有观察到这种变化,与TAT基因表达不存在相关.
- 许多体内观察到的二甲基硫酸盐活性变化在体内被克隆的DNA和纯化的受体复制.
结论:
- 激素结合对于葡萄糖皮质体受体与其在氨酸转移酶基因中的DNA结合位点 (GREs) 的体内相互作用至关重要.
- 这些发现挑战了预先结合的概念,在没有这种特定系统的激素的情况下转录活跃的受体.
- 这项研究强调了激素诱导的结构变化对受体-DNA参与转录激活的重要性.
相关概念视频
Intracellular Hormone Receptors
Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
Internal Receptors
Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Co-activators and Co-repressors
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...
Co-activators and Co-repressors
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...
Diversity in Cell Signaling Responses
The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity.
Graded and Abrupt Responses
Some signaling systems generate...
Graded and Abrupt Responses
Some signaling systems generate...
Signal Transduction: Overview
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...


