Galdieri Luciano, Zhang Tiantian, Rogerson Daniella, Lleshi Rron, Vancura Ales
Department of Biological Sciences, St. John's University, Queens, New York, USA.
Department of Biological Sciences, St. John's University, Queens, New York, USA
Eukaryot Cell. 2014 Dec;13(12):1472-83. doi: 10.1128/EC.00189-14. Epub 2014 Oct 17.
Cells sense and appropriately respond to the physical conditions and availability of nutrients in their environment. This sensing of the environment and consequent cellular responses are orchestrated by a multitude of signaling pathways and typically involve changes in transcription and metabolism. Recent discoveries suggest that the signaling and transcription machineries are regulated by signals which are derived from metabolism and reflect the metabolic state of the cell. Acetyl coenzyme A (CoA) is a key metabolite that links metabolism with signaling, chromatin structure, and transcription. Acetyl-CoA is produced by glycolysis as well as other catabolic pathways and used as a substrate for the citric acid cycle and as a precursor in synthesis of fatty acids and steroids and in other anabolic pathways. This central position in metabolism endows acetyl-CoA with an important regulatory role. Acetyl-CoA serves as a substrate for lysine acetyltransferases (KATs), which catalyze the transfer of acetyl groups to the epsilon-amino groups of lysines in histones and many other proteins. Fluctuations in the concentration of acetyl-CoA, reflecting the metabolic state of the cell, are translated into dynamic protein acetylations that regulate a variety of cell functions, including transcription, replication, DNA repair, cell cycle progression, and aging. This review highlights the synthesis and homeostasis of acetyl-CoA and the regulation of transcriptional and signaling machineries in yeast by acetylation.
细胞能够感知其周围环境中的物理条件和营养物质的可利用性，并做出适当反应。这种对环境的感知以及随之而来的细胞反应是由众多信号通路精心调控的，通常涉及转录和代谢的变化。最近的发现表明，信号传导和转录机制受源自代谢并反映细胞代谢状态的信号调控。乙酰辅酶A（CoA）是一种关键代谢物，它将代谢与信号传导、染色质结构和转录联系起来。乙酰辅酶A由糖酵解以及其他分解代谢途径产生，并用作柠檬酸循环的底物以及脂肪酸和类固醇合成及其他合成代谢途径中的前体。其在代谢中的核心地位赋予了乙酰辅酶A重要的调节作用。乙酰辅酶A作为赖氨酸乙酰转移酶（KATs）的底物，催化将乙酰基转移到组蛋白和许多其他蛋白质中赖氨酸的ε-氨基上。乙酰辅酶A浓度的波动反映了细胞的代谢状态，这种波动转化为动态的蛋白质乙酰化，从而调节多种细胞功能，包括转录、复制、DNA修复、细胞周期进程和衰老。本综述重点介绍了乙酰辅酶A的合成与稳态以及酵母中乙酰化对转录和信号传导机制的调控。
