通过核受体/特异性蛋白 (Sp) 相互作用激活癌症中的基因
Stephen Safe1, Evan Farkas1, Amanuel E Hailemariam1
1Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA.
Cancers
|January 25, 2025
概括
核受体 (NR) 和 Sp 转录因子 (TF) 形成复合体,间接调节基因表达. 这种NR/Sp复杂相互作用为各种疾病提供了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 人类核受体 (NR) 超级家族包括48个关联体激活的转录因子,这些因子对细胞平衡和疾病至关重要.
- NRs是关键的药物标,配体通过激动剂,抗剂或逆激动剂调节基因表达.
- 经典的NR机制涉及DNA以单体,二元体或异构体的形式与反应元素结合.
研究的目的:
- 通过核受体 (NR) 间接联合调节的Sp调节基因.
- 阐明NR-Sp复合体形成和基因调节中的功能机制.
- 突出针对NR-Sp相互作用的治疗潜力.
主要方法:
- 对NR调节基因和转录因子结合现有研究的审查.
- 对NR和Sp转录因子结合位点的促进器区域的分析.
- 研究NR-Sp复合体的形成及其对基因表达的影响.
主要成果:
- 许多NR调节基因缺乏直接的NR元素结合;它们的促进体结合了Sp1,Sp3和Sp4转录因子.
- 核受体直接结合Sp1,Sp3或Sp4,形成NR/Sp复合体,结合富含GC的位点.
- 响应NR的基因含有结合SpTF和NR的cis元素,突变会影响诱导性和基底表达.
结论:
- NRs的基因调节通常涉及通过Sp转录因子的间接联合调节.
- NR/Sp复合体作为基因表达的关键调解者,受NR配体的影响.
- 向NR或诱导SpTF降解对NR响应基因具有双重的治疗策略.
相关概念视频
Transducer Mechanism: Nuclear Receptors
1.3K
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:
1.3K
Signal Transduction: Overview
8.2K
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...
8.2K
Co-activators and Co-repressors
7.2K
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...
7.2K
RNA Polymerase II Accessory Proteins
9.1K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.1K
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
Epigenetic Regulation
3.0K
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...
3.0K


