通过核激素受体之间的全相互作用,建立了独特的反应途径
B M Forman1, K Umesono, J Chen
1Salk Institute for Biological Studies, San Diego, California, USA.
Cell
|May 19, 1995
概括
核受体异构体,如那些涉及9-cis视网膜酸受体 (RXR) 的异构体,可以表现出独特的荷尔蒙反应. 体相互作用创造了多样化的激素反应网络.
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 遗传学 是一个
背景情况:
- 异种化是真核转录因子的一个基本机制.
- 9-cis视网膜酸受体 (RXR) 是核受体的共同伙伴,如甲状腺激素受体 (T3R) 和视网膜酸受体 (RAR).
研究的目的:
- 研究RXR与其他核受体合作时的转录特性.
- 为了确定含有RXR的异构体是否表现出双重激素反应.
主要方法:
- 开发了一种策略,以评估单独和异构体中的受体活性.
- 研究了各种RXR异构体的转录活性,包括具有T3R,RAR和NGFI-B/Nurr1.1的异构体.
主要成果:
- 在T3R-RXR和RAR-RXR异构体中,RXR的内在DNA结合被抑制.
- 与NGFI-B/Nurr1孤儿受体一起,RXR作为非DNA结合的辅因子起作用.
- 与NGFI-B/Nurr1的异体化形成了一个新的荷尔蒙依赖复合体.
结论:
- 异构体内的异构体相互作用会产生具有不同性质的复合体.
- 在激素反应网络中观察到的多样性中,Allostery是至关重要的.
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.
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.
Types of Receptors: Internal Receptors
Many cellular signals are hydrophilic and cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind intracellular receptors that reside within the cell cytoplasm or nucleus. Many mammalian steroid hormones and nitric oxide (NO) gas use this cell signaling mechanism.
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Transducer Mechanism: Nuclear Receptors
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:
Target Cell Response to Hormones
Hormones intricately bind to receptors on the surface or within target cells, initiating a cascade of cellular responses.
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...
Notably, the cellular response can be regulated by altering the number of receptors expressed in the cell. For example, prolonged exposure to elevated hormone levels results in a gradual decline or down-regulation in the number of receptors for that specific hormone on the cell surface. Conversely, in response to low hormone levels, cells may use up-regulation, producing an...


