AhR-分子伴侣复合物的组成部分因配体是否有毒或无毒而有所不同
Yukihiko Narita1, Arisa Tamura2, Shiori Hatakeyama2
1Department of Neurosurgery, Akita University Graduate School of Medicine, Japan.
FEBS letters
|April 11, 2024
概括
基碳化合物受体 (AhR) 根据连接体形成不同的分子伴侣复合体. 与毒性联体相比,DHNA与AhR的结合导致了独特的复杂和较慢的核转位.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
背景情况:
- 基碳化合物受体 (AhR) 是一种由联体激活的转录因子.
- 在接触有毒化合物时,AhR通常与HSP90,XAP2和p23伴侣形成复合体.
- 1,4-二基-2-纳酸 (DHNA) 已被确定为一种新的AhR连接体.
研究的目的:
- 为了研究当DHNA与AhR结合时形成的分子伴侣复合物的组成.
- 为了比较DHNA诱导的AhR激活机制与有毒配体诱导的AhR激活机制.
主要方法:
- 使用3-甲基三烯 (3-MC) 和DHNA分离AhR相关蛋白的亲和染色学.
- 分析化伴侣复合体内的蛋白质成分.
- 用3-MC或DHNA治疗的细胞中AhR核转位的时间分析.
主要成果:
- 从3-MC亲和系列中化出来的蛋白质显示出正规的AhR-HSP90-XAP2-p23复合体.
- 来自DHNA亲和系列的化物显示出AhR-HSP90-XAP2复合体,特别是缺乏p23.
- 在3MC处理的细胞中,AhR的核转位是快速的 (30分钟内),但在DHNA处理的细胞中显著慢 (从60分钟开始).
结论:
- AhR-分子伴侣复合物的组成因配体而异.
- DHNA与AhR结合导致一个独特的复合体和延迟的核转移.
- 这些发现表明,AHR激活机制在DHNA和有毒配体之间有所不同.
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