雄激素受体无处不在化将KCTD13与生殖尿路缺陷联系起来
Ahmed Chahdi1,2, Carolina Jorgez3, Jill A Rosenfeld4
1Department of Surgery, Nemours Children's Health, Orlando, Florida, USA.
概括
含有13 (KCTD13) 蛋白质的通道四化域调节受体 (AR) 无处不在. KCTD13 的时间.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 含有13 (KCTD13) 的通道四重化域是基于库林3的E3无素连接酶的适配蛋白.
- 在KCTD13中拷贝数变异与生殖尿路异常有关.
- 雄激素受体 (AR) 信号传递对男性生殖发育至关重要.
研究的目的:
- 调查KCTD13在调节雄激素受体 (AR) 无化和功能的作用.
- 阐明KCTD13通过不同的E3结合酶介导的AR泛基化影响的机制.
- 了解KCTD13缺乏对AR基因表达的影响.
主要方法:
- 西方涂抹以评估蛋白质水平和无处不在.
- 同免疫沉试验用于研究蛋白质与蛋白质相互作用.
- 定量PCR用于测量基因表达.
- 使用重组蛋白和KCTD13突变体 (KCTD13 ΔBTB) 的实验.
主要成果:
- 在小鼠中,KCTD13缺乏导致AR泛化增加,丸中AR蛋白水平降低.
- KCTD13增强了CUL3依赖的AR泛化,但没有影响CUL3与AR结合.
- 通过破坏AR/STUB1复合体,KCTD13抑制了STUB1介导的AR泛化,需要其BTB域.
- KCTD13增加了AR目标基因FOXJ1.1的表达.
结论:
- KCTD13在调节AR无化方面发挥着双重作用,作为CUL3的适配器和STUB1.1的抑制剂.
- KCTD13的BTB域对于其与AR和STUB1的相互作用至关重要,它调解了AR/STUB1复合物的解离.
- KCTD11缺乏导致AR泛化和降解的增加,影响AR信号传递,并可能导致生殖尿路异常.
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