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

Abstract

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. protein prenylation, GGPP, FPP, biological function regulation Citation:Xu N, Shen N, Wang XX, Jiang S, Xue B, Li CJ. Protein prenylation and human diseases: a balance of protein farnesylation and geranylgeranylation.

Alteration of RhoA Prenylation Ameliorates Cardiac and Vascular Remodeling in Spontaneously Hypertensive Rats

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“…Therefore, the two pathways are expected to influence each other. Pathological aspects of prenylations are found in various conditions such as insulin sensitivity, inflammation, cardiac hypertrophy, hepatic lipogenesis [223]. Therefore, development of inhibitors to FTase and GGTase-I would serve therapeutic purposes.…”

Transcriptomics and proteomics in studies of induced differentiation of leukemia cells

“…Присоединение гидрофобных групп приводит к изменению физико-химических свойств белков и влияет на белок-белковые взаимодействия, а также на взаимодействие белков с мембраной. Пренилирование Ras белков вовлечено в развитие злокачественных новообразований различных типов, включая колоректальную карциному, меланому, карциному простаты и гепатоцеллюлярную карциному [62,63]. Вероятно, пренилирование задействовано и в формировании лейкозного фенотипа.…”