Fucosylation pathway

Fucosylation is a post-translational modification in which fucose is transferred to glycoproteins, glycolipids, or polysaccharides, predominantly by a family of enzymes called fucosyltransferases[1][3][5]. The process uses GDP-fucose as a donor substrate, generated either through a de novo synthesis pathway from GDP-mannose or via a salvage pathway from free fucose[1][3]. Fucosylation regulates diverse biological processes including protein folding, immune cell trafficking, host–pathogen interactions, and signal transduction (notably Notch and TGF-β receptor function)[1][3][5]. Aberrations in the pathway, especially altered expression of enzymes like FUT8, are implicated in cancer progression, metastasis, therapy resistance, and serve as biomarkers in oncology[2][3][4][5]. While the fucosylation process itself is not a single molecular target, specific pathway enzymes—particularly fucosyltransferases—are explored as drug targets, with inhibitors like Morusinol under preclinical study for cancer indications[2]. Disruption of fucosylation can cause developmental defects and immunological abnormalities, reflecting the pathway’s broad physiological role[1][3][5].

Other names

Fucose biosynthetic pathwayGDP-fucose synthesis pathwayProtein fucosylation

Enzyme inhibition (fucosyltransferase inhibitors block fucose addition to glycoproteins/lipids); Modulation of N-glycan core fucosylation alters receptor function and cell signaling