Protein prenylation and human diseases: a balance of protein farnesylation and geranylgeranylation  

作　　者：XU Na SHEN Ning WANG XiuXing JIANG Shan XUE Bin LI ChaoJun 

机构地区：[1]Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and Medical School of Nanjing University, National Resource Center for Mutant Mice

出　　处：《Science China(Life Sciences)》2015年第4期328-335,共8页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China(2012CB524900,2009CB918703);National Natural Science Foundation of China(31271540,30671086)awarded to Li Chao Jun

摘　　要：The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate(FPP) or geranylgeranyl pyrophosphate(GGPP) as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess Caa X motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase(GGPPS) catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.The protein prenylation is one of the essential post-translational protein modifications, which extensively exists in the eukaryocyte. It includes protein farnesylation and geranylgeranylation, using farnesyl pyrophosphate （FPP） or geranylgeranyl pyrophosphate （GGPP） as the substrate, respectively. The prenylation occurs by covalent addition of these two types of isoprenoids to cysteine residues at or near the carboxyl terminus of the proteins that possess CaaX motif, such as Ras small GTPase family. The attachment of hydrophobic prenyl groups can anchor the proteins to intracellular membranes and trigger downstream cell signaling pathway. Geranylgeranyl biphosphate synthase （GGPPS） catalyzes the synthesis of 20-carbon GGPP from 15-carbon FPP. The abnormal expression of this enzyme will affect the relative content of FPP and GGPP, and thus disrupts the balance between protein farnesylation and geranylgeranylation, which participates into various aspects of cellular physiology and pathology. In this paper, we mainly review the property of this important protein post-translational modification and research progress in its regulation of cigarette smoke induced pulmonary disease, adipocyte insulin sensitivity, the inflammation response of Sertoli cells, the hepatic lipogenesis and the cardiac hypertrophy.

关 键 词：protein prenylation GGPP FPP biological function regulation 

分 类 号：R3411[医药卫生—基础医学]