BAP1调节IP3R3介导的Ca2+流向线粒体,抑制细胞转化
Angela Bononi1, Carlotta Giorgi2, Simone Patergnani2
1University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii 96813 USA.
Nature
|June 15, 2017
概括
BRCA1关联蛋白1 (BAP1) 突变会损害其核和细胞质功能,导致癌症. 降低BAP1水平防止DNA损伤后的亡,促进载体的瘤发育.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- BRCA1关联蛋白1 (BAP1) 是一种瘤抑制剂,对基因组完整性至关重要.
- 遗传的BAP1突变 (BAP1+/-) 会导致各种癌症,包括间皮瘤和皮膜黑色素瘤.
- BAP1在DNA修复中的核作用已经确立,但其细胞质功能仍然不清楚.
研究的目的:
- 为了研究BAP1.1未知的细胞质功能.
- 阐明BAP1在细胞对DNA损伤和环境致癌物质反应中的作用.
- 了解BAP1+/-载体癌症发展的机制基础.
主要方法:
- 定位研究以确定BAP1的亚细胞区.
- 生物化学测试以确定BAP1的相互作用伙伴和基质.
- 在具有不同BAP1水平的细胞中测量流量和亡测定.
- 基因毒性应激暴露后细胞转变的评估.
主要成果:
- 发现BAP1定位在内质网膜中.
- BAP1结合,二二基化,并稳定了3型内醇三酸盐受体 (IP3R3).
- 降低BAP1水平会损害DNA损伤后的释放和亡诱导,增加细胞转化速率.
结论:
- BAP1在内细胞网中的细胞质活性对于诱导亡和瘤抑制至关重要.
- 核和细胞质BAP1功能的缺陷有助于BAP1+/-载体的癌症发展.
- 在致癌过程中,BAP1在调节基因与环境相互作用方面发挥着关键作用.
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