SIRT7将H3K18脱乙化与维持瘤转化联系在一起
Matthew F Barber1, Eriko Michishita-Kioi, Yuanxin Xi
1Department of Biology, Stanford University, Stanford, California 94305, USA.
Nature
|June 23, 2012
概括
SIRT7是一种组织素脱乙酶,通过脱乙H3K18Ac. 稳定癌细胞. 削弱SIRT7减少瘤生长,突出其在癌症进展中的作用和作为治疗点的潜力.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 癌症研究 癌症研究
背景情况:
- 赛尔图因是调节细胞通路,代谢和衰老的蛋白质.
- 哺乳动物sirtuin 7 (SIRT7) 的特定功能和标以前尚不清楚.
- 基因组乙化,特别是H3K18Ac,与细胞转化和癌症预后有关.
研究的目的:
- 阐明SIRT7.7的生物化学活性和生理功能.
- 确定SIRT7在稳定癌细胞转化状态中的作用.
- 研究SIRT7对染色质调节和瘤形成的影响.
主要方法:
- 生物化学测试以确定SIRT7的酶活性作为NAD ((+) 依赖的H3K18Ac脱乙酶.
- 全基因组结合研究用于映射SIRT7基因促进体.
- 试验涉及SIRT7在人类癌细胞和老鼠异种移植中的耗尽.
主要成果:
- 在特定的基因促进体上,SIRT7 deacetylates H3K18Ac,导致转录抑制.
- SIRT7与ELK4的相互作用会影响其基因谱,包括瘤抑制基因.
- SIRT7对于癌细胞特征至关重要,如结独立生长和逃避接触抑制,并在耗尽时减少瘤异种移植的生长.
结论:
- SIRT7是一种高度选择性的H3K18Ac脱乙酶,对于维持癌细胞转化至关重要.
- SIRT7在染色质调节和细胞转化程序中发挥着关键作用.
- 在体内瘤形成中,SIRT7是必不可少的,这表明它有可能成为治疗点.
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