ZEB1通过K811乙化来调节,以促进稳定性,NuRD复杂相互作用,EMT和NSCLC转移
Mabel Perez-Oquendo1,2, Roxsan Manshouri1,2, Yanhua Tian1,2
1Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Molecular cancer research : MCR
|May 31, 2023
概括
指 E-box-binding homeobox 1 (ZEB1) 在K811的乙化增强了它的稳定性,并促进了肺癌的转移. 这种乙化对ZEB1至关重要.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 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:
- 皮质到介质细胞的过渡 (EMT) 驱动癌症的入侵和转移.
- 指 E-box-binding homeobox 1 (ZEB1) 是EMT中的一个关键的转录抑制剂.
- ZEB1表现出可变的分子重量,表明了翻译后修饰 (PTMs).
研究的目的:
- 为了确定ZEB1.1.的新型PTM.
- 在非小细胞肺癌 (NSCLC) 中研究K811处ZEB1乙化的功能作用.
主要方法:
- 质谱测量用于识别ZEB1 PTMs.
- 在NSCLC细胞系中生成ZEB1乙模仿 (K811Q) 和乙缺乏 (K811R) 突变体.
- 蛋白质稳定性测试,NuRD复杂相互作用研究和RNA测序.
主要成果:
- 鉴定出K811乙化是一种新型ZEB1 PTM.
- 与野生类型和K811Q ZEB1.1相比,K811R ZEB1的蛋白质稳定性降低.
- 乙化ZEB1 (WT和K811Q) 招募了NuRD复杂和下调的上皮基因,促进了入侵和转移.
- K811R ZEB1未能促进肺腺癌的入侵和转移.
结论:
- K811乙化稳定了ZEB1蛋白质.
- ZEB1乙化增强了它与NuRD复合体的相互作用.
- 通过EMT,ZEB1乙化促进了肺腺癌转移.
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