在新的皮里米丁生物合成复合物中,它们支持癌细胞的增殖和铁亡防御
Chuanzhen Yang1, Yiliang Zhao1, Liao Wang1,2
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Nature cell biology
|June 8, 2023
概括
研究人员发现了一种新的多酶复合体,称为pyrimidinosome,它调节了pyrimidine生物合成和ferroptosis. 这种复合物是癌症治疗的潜在目标,特别是在AMP激活蛋白激酶 (AMPK) 表达率低的细胞中.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 胺新生态合成涉及细胞酶CAD和UMPS以及线粒体DHODH.
- 这些酶在皮里米丁合成中的编排和调节仍然不清楚.
- 铁亡是一种受调节的细胞死亡形式,与代谢途径有关.
研究的目的:
- 阐明参与新型金胺生物合成的酶的组织结构.
- 调查控制胺流的调节机制及其与铁亡的联系.
- 探索针对癌症中新发现的这种复合体的治疗潜力.
主要方法:
- 蛋白质复合体共免疫沉和聚类分析.
- 酶活性测定用于皮里米丁合成.
- 细胞测试以评估铁和药物敏感性.
- 西方涂抹分析蛋白质表达,包括AMPK.
主要成果:
- 确定了一种称为"pyrimidinosome"的多酶复合体,包括细胞质CAD,UMPS和线粒体DHODH.
- 谷氨酸氧化乙酸转胺酶1和电压依赖的阴离子选择性通道蛋白3介导着胺体的组装.
- AMP激活蛋白激酶 (AMPK) 调节皮里米丁酶组合,并影响铁亡防御.
- 减少AMPK表达的癌细胞显示出对pyrimidinosome的依赖性增加,并且更容易受到其抑制.
结论:
- 胺酶组合了细胞和线粒体酶,以实现高效的胺生物合成.
- 这种复合体在调节金胺代谢流和铁亡中起着至关重要的作用.
- 向pyrimidinosome为癌症治疗提供了一个有希望的治疗策略,特别是在AMPK缺乏的瘤中.
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