环素D1广泛重编程新陈代谢,以支持肝细胞中的生物合成途径
Heng Wu1, Betsy T Kren2, Andrew N Lane3
1Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota, USA.
The Journal of biological chemistry
|December 28, 2023
概括
环素D1通过促进必不可少的生物合成途径,如糖解和胺合成,驱动细胞增殖. 针对这种细胞循环调节器及其下游效应提供了潜在的抗癌策略.
科学领域:
- 细胞代谢的细胞代谢.
- 癌症生物学 癌症生物学
- 分子瘤学分子瘤学
背景情况:
- 细胞增殖需要对生物合成进行代谢重编程.
- 细胞循环调节剂与代谢途径之间的联系尚不清楚.
- 环素D1 (细胞循环调节剂和瘤基因) 在癌症中经常过度表达.
研究的目的:
- 调查环素D1在肝细胞增殖过程中对生物合成代谢的新效应.
- 阐明循环素D1影响代谢途径的机制.
主要方法:
- 用代谢和蛋白质组分析来研究代谢变化.
- 实验室试验用于检查代谢酶的酸化由环D1/Cdk4.4.
- 在癌细胞中测试了Cdk4和dihydroorotate脱酶的药理抑制.
主要成果:
- 发现Cyclin D1可以促进糖解,酸路径和核酸合成.
- 环素D1直接与代谢酶结合并激活,包括糖解中的阿尔多酶和GAPDH.
- 胺新生合成高度依赖于环林D1,该酶酸化CAD酶.
- 抑制Cdk4和二基酸脱酶协同减少肝细胞癌细胞增殖和存活率.
结论:
- 环素D1广泛促进肝细胞中的关键生物合成途径.
- 这项研究揭示了cyclin D1在代谢重编程中的作用,并表明癌细胞中潜在的代谢脆弱性.
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