雄激素受体 雄激素受体
Greg Van-Duyne1, Ian A Blair2, Cynthia Sprenger3
1Department of Biophysics & Biochemistry, Perelman School of Medicine University of Pennsylvania, Philadelphia, PA, United States.
雄激素受体 (AR) 调节男性性激素功能,是药物点. 了解AR信号的进步,包括其蛋白质形式和抵抗机制,提供了新的治疗策略.
科学领域:
- 分子内分泌学分子内分泌学
- 信号通道的信号通道
- 核受体超级家族 核受体超级家族
背景情况:
- 雄激素受体 (AR) 是男性性发育和功能的关键转录因子.
- AR与内源性配体表现出悖论性效应,并与其他核受体共享反应元素,造成复杂性.
- 全长AR (AR-FL) 的高分辨率结构数据由于N端域 (NTD) 失序而具有挑战性.
研究的目的:
- 审查最近在理解雄激素受体 (AR) 信号通路方面的进展.
- 通过翻译后修饰和蛋白形来探索AR功能的调节.
- 在前列腺癌等疾病中讨论与AR相关的治疗策略和抵抗机制.
主要方法:
- 关于雄激素受体 (AR) 结构,功能和信号传导的当前文献的综述.
- 对翻译后修改及其对AR蛋白质形式的影响的分析.
- 检查耐药性机制和潜在的治疗干预措施.
主要成果:
- AR功能是由各种由翻译后修改产生的蛋白质形式调节的.
- 多蛋白质复合体内的相互作用决定了AR的转录输出.
- 前列腺癌的耐药性与AR上调和LBD缺乏的拼接变体有关.
结论:
- 用选择性雄激素受体调节剂 (SARMS) 或对抗剂向AR是治疗AR驱动疾病的关键.
- 像双极性T治疗和NTD-对抗剂这样的新策略在克服AR药物耐药性方面显示出希望.
- 对AR信号复杂性的进一步研究对于开发更有效的疗法至关重要.
更多相关视频
10:51Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
08:36Prostate Organoid Cultures as Tools to Translate Genotypes and Mutational Profiles to Pharmacological Responses
Published on: October 24, 2019
相关概念视频
Types of Receptors: Internal Receptors
Similar to membrane-bound receptors, the binding of a ligand to the intracellular receptor of causes a conformational change in the...
Internal Receptors
Intracellular Hormone Receptors
Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Transducer Mechanism: G Protein–Coupled Receptors
GPCRs are also called heptahelical,...
