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乙烯基转移酶P300 通过催化乳糖化在肺癌中调节葡萄糖代谢重编程
Qingzhi Ma1, Qingmei Zeng1, Kun Wang1
1Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an 710032, China.
International journal of molecular sciences
|January 23, 2024
概括
这项研究显示,p300充当了氨酸糖化 (Ksucc) 的"编写器",促进了癌细胞代谢. 这一发现对于了解肺腺癌 (LUAD) 进展和潜在的治疗点至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 异常蛋白质的翻译后修改是癌症的特征.
- 氨酸糖化 (Ksucc) 对癌细胞能量代谢至关重要.
- 乙转移酶p300在催化化中的作用以前是未知的.
研究的目的:
- 为了调查p300是否催化了氨酸糖化.
- 确定p300介导的Ksucc在肺腺癌 (LUAD) 细胞代谢和进展中的作用.
- 探索p300在LUAD中的临床相关性.
主要方法:
- 糖胺分析以确定p300-糖化蛋白质.
- 基因缺失和EP300和PGK1.1的特定位点突变.
- 在体内进行代谢分析.
- 在LUAD患者组织中分析p300表达.
主要成果:
- 确定p300为Ksucc的"编写器",EP300的缺陷降低了全球Ksucc水平.
- 在细胞质碳水化合物代谢途径中,p300-succinylated 蛋白质得到了丰富.
- 在PGK1上删除EP300和Ksucc位点的突变损害了糖解和乳酸生产.
- 在LUAD组织中高细胞质p300水平与晚期和不良预后相关.
结论:
- p300催化了氨酸酸化,促进了LUAD中的葡萄糖代谢重编程.
- 通过p300介导的Ksucc有助于肺癌恶性进展.
- p300 是一个潜在的 LUAD 预后和治疗点的生物标志物.
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