PDF(Pubmed)
Abstract：
Nucleotides are the foundational elements of life. Proliferative cells acquire nutrients for energy production and the synthesis of macromolecules, including proteins, lipids, and nucleic acids. Nucleotides are continuously replenished through the activation of the nucleotide synthesis pathways. Despite the importance of nucleotides in cell physiology, there is still much to learn about how the purine and pyrimidine synthesis pathways are regulated in response to intracellular and exogenous signals. Over the past decade, evidence has emerged that several signaling pathways [Akt, mechanistic target of rapamycin complex I (mTORC1), RAS, TP53, and Hippo-Yes-associated protein (YAP) signaling] alter nucleotide synthesis activity and influence cell function. Here, we examine the mechanisms by which these signaling networks affect de novo nucleotide synthesis in mammalian cells. We also discuss how these molecular links can be targeted in diseases such as cancers and immune disorders.
摘要：
核苷酸是生命的基本要素。增殖细胞获得营养物质的能量生产和大分子的合成，包括蛋白质，脂质，和核酸。通过核苷酸合成途径的激活来持续补充核苷酸。尽管核苷酸在细胞生理学中很重要，关于嘌呤和嘧啶合成途径如何响应于细胞内和外源信号而受到调节，仍有很多需要了解。在过去的十年里，证据已经出现了几种信号通路[Akt，雷帕霉素复合物I（mTORC1）的机制靶标，RAS,TP53和Hippo-Yes相关蛋白（YAP）信号传导]改变核苷酸合成活性并影响细胞功能。这里,我们研究了这些信号网络影响哺乳动物细胞从头核苷酸合成的机制。我们还讨论了这些分子联系如何在癌症和免疫疾病等疾病中成为目标。
