非蛋白质溶解性ubiquitination通过NCoR/SMRT/HDAC3核心压缩复合物调节乳腺癌细胞MCF-7中的染色质占用
Giulio Ferrero1, Maria Dafne Cardamone2, Francesca Luca1,2
1Department of Clinical and Biological Science, University of Torino, Orbassano (Torino) 10043, Italy.
概括
这项研究揭示了G蛋白通路抑制剂2 (GPS2) 和瘤缩因子受体相关因子6 (TRAF6) 如何协调基因表达调节. 核TRAF6控制辅因子的活动和局部化,影响细胞平衡和炎症.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 基因表达受到转录因子和辅因子的严格调节,其活动由信号转导通路调节.
- 控制辅因子活动和在亚细胞领域的局部化的精确机制尚未完全理解.
- G-蛋白通路抑制剂2 (GPS2) 是一个关键的转录辅因子,参与细胞平衡,调节线粒体生物发生,应激反应,脂质代谢,胰岛素信号和炎症.
研究的目的:
- 研究GPS2在MCF-7乳腺癌细胞内调节基因表达中的作用.
- 为了阐明GPS2,TRAF6和核心压力复合体之间的相互作用,以响应炎症信号.
主要方法:
- 生物化学分析,全基因组RNA测序和染色体免疫沉-Seq (ChIP-Seq) 的整合.
- 蛋白质与蛋白质相互作用和无处不在事件的分析.
- 研究从染色质中招募和清除辅因子.
主要成果:
- 核GPS2对于基因素脱乙酶3 (HDAC3) 招募到染色质是必不可少的,通过TRAF6依赖的无处不在介导.
- 瘤亡因子受体相关因子6 (TRAF6),一种E3泛素联酶,在IL-1β刺激时意外转移到核中.
- 核TRAF6与NCoR/SMRT核心压缩机相互作用,并通过TAB2的无处不在促进核心压缩机从监管区域的清除.
结论:
- 揭示了一个新的机制,其中核TRAF6协调辅因子活动和局部化与炎症信号.
- 展示了TRAF6介导的无处不在如何调节转录辅因子的动态招募和清除.
- 突出了信号转导途径和维持细胞平衡的表观遗传调节之间的复杂交互.
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