与SUMO1相关的SUMOylation和p65的酸化之间的相互作用促进肝细胞癌进展
Can Jiang1, Chunyang Zhang1, Min Dai1
1School of Basic Medical Sciences, Anhui Medical University, Hefei, China; Biopharmaceutical Institute, Anhui Medical University, Hefei, China.
Biochimica et biophysica acta. Molecular cell research
|September 20, 2023
概括
小型泛素相关修饰剂1 (SUMO1) 核因子kappaB (NF-κB) 亚单元p65的SUMOylation增强了肝细胞癌 (HCC) 的进展. SUMO1 增强了 p65 的核进口和活动,促进了 HCC 细胞的活力和侵入性.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 生物化学 生物化学
背景情况:
- 核因子kappaB (NF-κB) 下单元p65对于肝细胞癌 (HCC) 的进展至关重要.
- p65酸化正面调节NF-κB活动.
- 小型无素相关修饰剂1 (SUMO1) SUMOylation of p65促进核进口和HCC进展,但其对转录活性和酸化相互作用的影响尚不清楚.
研究的目的:
- 研究SUMO1-介导的p65 SUMOylation对NF-κB转录活性的影响.
- 阐明p65酸化与HCC中的SUMOylation之间的关系.
- 探索p65在HCC中潜在的致癌机制.
主要方法:
- 在HCC患者组织中分析p65酸化和SUMO1表达.
- 在体外SUMOylation试验和p65SUMOylation/酸化突变体的构建.
- 评估肝瘤细胞活力,入侵和亡.
- 在SUMO1,p65酸化和SUMOylation之间的相关性分析.
主要成果:
- 在HCC组织中增加了化p65和SUMO1水平,它们之间存在正相关性.
- 过度表达SUMO1可以调节酸化p65水平.
- 通过SUMO1介导的p65SUMOylation增强了p65核导入和NF-κB活动.
- 通过SUMO1介导的p65SUMOylation和p65酸化 (S276) 增加了肝瘤细胞活力/入侵,并降低了细胞亡.
- p65酸化促进了SUMO1介导的p65 SUMOylation,而SUMO1介导的p65 SUMOylation在S276.6上调节了p65酸化.
结论:
- 通过SUMO1介导的p65SUMOylation和p65酸化是HCC进展的关键驱动因素.
- 在p65酸化和SUMO1介导的p65SUMOylation之间存在一个积极的反循环,增强了致癌活性.
- 了解这些翻译后的修改为HCC提供了潜在的治疗点.
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