Regulatory Roles of Metabolites in Cell Signaling Networks  

作　　者：Feng Li Wei Xu Shimin Zhao 

机构地区：[1]State Key Lab of Genetic Engineering,Fudan University [2]Institutes of Biomedical Sciences,Fudan University

出　　处：《Journal of Genetics and Genomics》2013年第7期367-374,共8页遗传学报（英文版）

基　　金：supported by the National Key Basic Research Programs of China(Nos.2012CB910300, 2012CB721102,2013CB911204,and 2013CB945400);the National Natural Foundation of China(No.31030042);the Shanghai Basic Research Fund(Nos.11JC1401100 and 13XD 1400500).

摘　　要：Mounting evidence suggests that cellular metabolites, in addition to being sources of fuel and macromolecular substrates, are actively involved in signaling and epigenetic regulation. Many metabolites, such as cyclic AMP, which regulates phosphorylation/dephosphor- ylation, have been identified to modulate DNA and histone methylation and protein stability. Metabolite-driven cellular regulation occurs through two distinct mechanisms： proteins allosterically bind or serve as substrates for protein signaling pathways, and metabolites covalently modify proteins to regulate their functions. Such novel protein metabolites include fumarate, succinyl-CoA, propionyl-CoA, butyryl-CoA and crontonyl-CoA. Other metabolites, including α-ketoglutarate, succinate and fumarate, regulate epigenetic processes and cell signaling via protein binding. Here, we summarize recent progress in metabolite-derived post-translational protein modification and metabolite-binding associated signaling regulation. Uncovering metabolites upstream of cell signaling and epigenetic networks permits the linkage of metabolic disorders and human diseases, and suggests that metabolite modulation may be a strategy for innovative therapeutics and disease prevention techniques.Mounting evidence suggests that cellular metabolites, in addition to being sources of fuel and macromolecular substrates, are actively involved in signaling and epigenetic regulation. Many metabolites, such as cyclic AMP, which regulates phosphorylation/dephosphor- ylation, have been identified to modulate DNA and histone methylation and protein stability. Metabolite-driven cellular regulation occurs through two distinct mechanisms： proteins allosterically bind or serve as substrates for protein signaling pathways, and metabolites covalently modify proteins to regulate their functions. Such novel protein metabolites include fumarate, succinyl-CoA, propionyl-CoA, butyryl-CoA and crontonyl-CoA. Other metabolites, including α-ketoglutarate, succinate and fumarate, regulate epigenetic processes and cell signaling via protein binding. Here, we summarize recent progress in metabolite-derived post-translational protein modification and metabolite-binding associated signaling regulation. Uncovering metabolites upstream of cell signaling and epigenetic networks permits the linkage of metabolic disorders and human diseases, and suggests that metabolite modulation may be a strategy for innovative therapeutics and disease prevention techniques.

关 键 词：METABOLITE Signaling Modification BINDING EPIGENETICS 

分 类 号：R363[医药卫生—病理学]