来自美国约翰霍普金斯大学的研究人员发现SAICAR蛋白可能有助于癌细胞在营养有限的条件下协调其能量生成方式,从而得以正常生存。

-2012年11月23日《科学》

中文翻译


【题目】SAICAR蛋白激活丙酮酸激酶M2型异构体和促进癌细胞在葡萄糖限制的条件下生存

【译文】在癌细胞受胁迫条件下,丙酮酸激酶M2型异构体(PKM2)在癌细胞的生长和代谢重编程过程中起重要的作用。本研究发现嘌呤核苷酸从头合成途径的中间体——SAICAR(琥珀酰氨基咪唑酰胺核糖-5′-磷酸)能特异性的激活PKM2蛋白。在葡萄糖缺乏的条件下,胞内SAICAR的含量以振荡的形式升高,从而激活癌细胞中的PKM2。癌细胞中SAICAR的含量变化会影响胞内的能量水平、葡萄糖摄取和乳糖产生。SAICAR与PKM2的互作也能促进癌细胞在葡萄糖限制的条件下生存。不论葡萄糖是否缺乏,在正常成熟表皮细胞或纤维母细胞中都没有发现SAICAR的积累。这种别构调节可能解释了癌细胞如何协调不同的代谢途径来优化它们的生长方式,从而成功在营养有限的肿瘤微环境中生存。

英文原稿


[Title]: SAICAR Stimulates Pyruvate Kinase Isoform M2 and Promotes Cancer Cell Survival in Glucose-Limited Conditions

[Authors]:Kirstie E. Keller, Irene S. Tan, and Young-Sam Lee

[Abstract]: Pyruvate kinase isoform M2 (PKM2) plays an important role in the growth and metabolic reprogramming of cancer cells in stress conditions. Here, we report that SAICAR (succinylaminoimidazolecarboxamide ribose-5′-phosphate, an intermediate of the de novo purine nucleotide synthesis pathway) specifically stimulates PKM2. Upon glucose starvation, cellular SAICAR concentration increased in an oscillatory manner and stimulated PKM2 activity in cancer cells. Changes in SAICAR amounts in cancer cells altered cellular energy level, glucose uptake, and lactate production. The SAICAR-PKM2 interaction also promoted cancer cell survival in glucose-limited conditions. SAICAR accumulation was not observed in normal adult epithelial cells or lung fibroblasts, regardless of glucose conditions. This allosteric regulation may explain how cancer cells coordinate different metabolic pathways to optimize their growth in the nutrient-limited conditions commonly observed in the tumor microenvironment.

原文地址

http://www.sciencemag.org/content/338/6110/1069.abstract

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201302/science-saicar-pyruvate-kinase-isoform-m2-pkm2-cancer/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


七 × 4 =


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息