| 2004 |
FUT8 encodes an α-1,6-fucosyltransferase that catalyzes the transfer of fucose from GDP-fucose to N-acetylglucosamine in an α-1,6 linkage on N-glycans (core fucosylation); knockout of both FUT8 alleles in CHO cells completely abolishes core fucosylation of antibody Fc regions, dramatically enhancing FcγRIIIa binding and ADCC (~100-fold increase). |
Homologous recombination knockout in CHO cells, glycan analysis, FcγRIIIa binding assay, ADCC assay |
Biotechnology and bioengineering |
High |
15352059
|
| 2006 |
Crystal structure of human FUT8 at 2.6 Å resolution reveals three domains: an N-terminal coiled-coil (α-helical) domain, a GT-B fold catalytic domain with a Rossmann fold housing the GDP-fucose donor binding site, and a C-terminal SH3 domain; conserved residues in the Rossmann fold participate in donor substrate binding and catalysis. |
X-ray crystallography at 2.6 Å resolution |
Glycobiology |
High |
17172260
|
| 2005 |
FUT8 is a type II Golgi-localized membrane protein that follows a rapid equilibrium random kinetic mechanism; it strongly recognizes the base portion and diphosphoryl group of GDP-β-L-fucose as donor substrate; two conserved arginine residues play an important role in donor substrate binding. |
Large-scale recombinant protein production in baculovirus/insect cells, kinetic analysis, inhibition studies with GDP-fucose derivatives |
Glycobiology |
High |
16344263
|
| 2006 |
Core fucosylation by Fut8 is required for normal TGF-β1 receptor and EGF receptor signaling; Fut8-null mice show severe growth retardation and emphysema-like lung destruction due to dysregulated TGF-β1 receptor activation, overexpression of MMP12/MMP13, and downregulation of elastin; reintroduction of Fut8 rescues receptor-mediated signaling in null cells. |
Fut8 knockout mouse phenotyping, TGF-β1 therapeutic rescue experiment, gene reintroduction rescue in null cells |
Methods in enzymology |
High |
17132494
|
| 2006 |
Core fucosylation by Fut8 is required for normal LRP-1 scavenger/endocytic function; loss of Fut8 impairs LRP-1-mediated endocytosis of IGFBP-3, leading to markedly elevated serum IGFBP-3 in Fut8-null mice; reintroduction of Fut8 rescues endocytosis. |
Fut8 knockout mouse model, endocytosis assay, serum IGFBP-3 measurement, Fut8 gene reintroduction rescue |
Journal of biochemistry |
High |
16567404
|
| 2009 |
Fut8 is required for normal VEGFR-2 expression in the lung; knockdown of Fut8 suppresses VEGFR-2 mRNA and protein at the transcriptional level; loss of VEGFR-2 increases ceramide and apoptosis of septal epithelia and endothelia, contributing to emphysema-like changes in Fut8-/- mice. |
Fut8 KO mouse lung analysis, siRNA knockdown in A549/TGP49 cells, VEGFR-2 mRNA/protein quantification, TUNEL assay |
Journal of biochemistry |
High |
19179362
|
| 2012 |
Donor substrate GDP-fucose binding to FUT8 involves specific recognition of the guanine base by His363 and Asp453, tight binding of the pyrophosphate moiety, and simultaneous binding of Arg365 to both the β-phosphate and the fucose moiety; prior binding of GDP is required for optimal N-glycan acceptor recognition. |
STD NMR, SPR binding assays, in silico molecular docking and MD simulations based on structural analogy to cePOFUT |
Biochimica et biophysica acta |
Medium |
22982178
|
| 2013 |
α1,6-Fucosylation of activin receptors by Fut8 negatively regulates activin-mediated signaling (phospho-Smad2); knockdown of Fut8 in PC12 cells decreases α1,6-fucosylation of activin receptors and enhances activin-induced phospho-Smad2 and neurite formation, while restoring Fut8 reverses this; demonstrating a dual role for Fut8 in TGF-β versus activin signaling. |
siRNA knockdown in PC12 cells, phospho-Smad2 immunoblot, neurite formation assay, activin receptor lectin analysis, Fut8 re-expression rescue |
FASEB journal |
High |
23796784
|
| 2013 |
FUT8 overexpression inhibits hemoglobin production and erythroid differentiation; the donor substrate-binding domain and a flexible loop are essential for this inhibitory function; FUT8 expression is positively regulated by c-Myc and c-Myb during erythroid differentiation. |
Gene expression profiling, overexpression and shRNA knockdown in murine erythroleukemia and K562 cells, domain mutagenesis, hemoglobin assay, transferrin receptor/glycophorin A FACS |
Journal of biological chemistry |
High |
23609441
|
| 2016 |
Mammalian FUT8 is the sole enzyme responsible for GnT I-independent core fucosylation of high-mannose N-glycans (Man5GlcNAc2); knockdown of FUT8 in GnT I-/- HEK293S cells eliminates core fucosylation of high-mannose glycoforms, while FUT8 overexpression produces fully core-fucosylated oligomannose glycans. |
Lentivirus-mediated FUT8 knockdown and overexpression in HEK293S GnT I-/- cells, glycan analysis of recombinant EPO |
Journal of biological chemistry |
High |
27008861
|
| 2017 |
FUT8 mediates core fucosylation of TGF-β receptor complexes, enhancing TGF-β1 binding and downstream signaling to promote EMT and breast cancer invasion; FUT8 is transcriptionally upregulated during TGF-β-induced EMT, creating a positive feedback loop. |
shRNA/CRISPR KO and lentiviral overexpression, lectin blot, luciferase signaling assay, in vitro ligand binding assay, transwell invasion, mammary fat pad xenograft |
Breast cancer research : BCR |
High |
28982386
|
| 2017 |
FUT8 silencing suppresses melanoma invasion and tumor dissemination; L1CAM is identified as a glycoprotein target of FUT8 core fucosylation, and core fucosylation of L1CAM impacts its cleavage and ability to support melanoma invasion. |
Systems-based glycomics of patient samples, siRNA silencing, in vitro invasion assays, in vivo tumor dissemination model, glycoprotein target enrichment |
Cancer cell |
High |
28609658
|
| 2018 |
FUT8 modifies the α1,6-fucosylation of IGF-1R, and this core fucosylation regulates IGF-1-dependent activation of IGF-1R and downstream MAPK and PI3K/Akt signaling in trophoblastic cells; FUT8 knockdown suppresses trophoblast proliferation, EMT, migration, and invasion. |
siRNA knockdown in JAR/JEG-3 cells, immunoprecipitation of core-fucosylated IGF-1R, phospho-IGF-1R western blot, functional cell assays |
Placenta |
High |
30712666
|
| 2020 |
The C-terminal SH3 domain of FUT8 is essential for its enzymatic activity both in cells and in vitro; His-535 in the SH3 domain is the critical residue for activity; the SH3 domain also mediates partial trafficking of FUT8 to the cell surface; ribophorin I (RPN1), a subunit of the oligosaccharyltransferase complex, binds FUT8 in an SH3-dependent manner and stimulates FUT8 activity and core fucosylation. |
Truncation mutants, site-directed mutagenesis, immunofluorescence, FACS, cell-surface biotinylation, proteomics, LC-ESI-MS, RPN1 siRNA knockdown |
Journal of biological chemistry |
High |
32350116
|
| 2020 |
FUT8-mediated core fucosylation of EGFR upregulates cell-surface EGFR and corresponding downstream signaling, contributing to castration resistance in prostate cancer; castration in xenograft models induces FUT8 overexpression which is associated with increased EGFR expression. |
FUT8 overexpression in prostate cancer cells, comprehensive proteomics, EGFR cell-surface quantification, androgen-depleted xenograft model |
Cancers |
Medium |
32085441
|
| 2020 |
FUT8 core fucosylation of EGFR promotes EGFR dimerization, EGF-EGFR complex trafficking, and AKT signaling; shRNA-mediated FUT8 knockdown reduces EGFR dimerization, slows EGF-EGFR complex trafficking, and decreases EGFR/AKT signaling, leading to reduced keratinocyte proliferation; conditional FUT8 knockout in an IL-23 psoriasis-like mouse model ameliorates disease phenotypes. |
shRNA knockdown, EGFR dimerization assay, EGF-EGFR trafficking assay, EGFR/AKT western blot, conditional KO mouse model |
Journal of investigative dermatology |
High |
32888953
|
| 2020 |
FUT8-mediated core fucosylation of EGFR in cancer-associated fibroblasts (CAFs) promotes their cancer-supporting capacity, leading to increased NSCLC cell proliferation and invasiveness in co-culture; FUT8 overexpression in CAFs promotes formation of an invasive tumor microenvironment in vivo. |
CAF isolation from NSCLC patients, FUT8 modulation, 3D-printed non-contact co-culture, CAF/NSCLC co-injection nude mouse model |
American journal of cancer research |
Medium |
32266093
|
| 2020 |
The α-helical (N-terminal coiled-coil) and SH3 domains of FUT8 are both required for enzymatic activity; FUT8 forms a homodimer via intermolecular hydrophobic interactions through its α-helical domains; the SH3 domain is located in close proximity to the α-helical domain in an intermolecular manner, as shown by in vivo disulfide cross-linking. |
Domain truncation and site-directed mutagenesis, in vivo disulfide cross-linking, heterologous expression in Sf21/COS-1 cells, enzymatic activity assays |
Biochimica et biophysica acta. General subjects |
High |
32147455
|
| 2020 |
FUT8 substrate specificity requires the biantennary complex N-glycan structure; FUT8 recognizes all sugar units of the G0 N-glycan and most residues of the Asn-X-Thr sequon; prior binding of GDP-β-L-fucose (or GDP) is required for optimal N-glycan acceptor recognition; the underlying peptide/protein context influences fucosylation of high-mannose and paucimannose but not complex-type N-glycans. |
Crystal structures of FUT8 with donor analog and four distinct glycan acceptors, STD NMR, kinetic assays on active site mutants, glycan acceptor library screening, CHO cell glycan engineering |
Journal of biological chemistry |
High |
33004438
|
| 2021 |
FUT8 catalyzes core fucosylation of B7H3 (CD276) at N-glycan sites, stabilizing B7H3 protein; FUT8 knockdown causes loss of B7H3 glycosylation and rescues B7H3-mediated immunosuppressive function in TNBC cells; combined FUT8 inhibition and anti-PDL1 shows enhanced therapeutic efficacy. |
FUT8 knockdown, glycan analysis, B7H3 protein stability assay, immune suppression functional assay, in vivo tumor model with 2F-Fuc inhibitor + anti-PDL1 |
Nature communications |
High |
33976130
|
| 2021 |
FUT8 overexpression in colonic cells increases delivery of MUC1 to the plasma membrane and extracellular release of MUC2 and MUC5AC; FUT8-modified mucins are more resistant to removal from the cell surface; FUT8 KD causes intracellular accumulation of MUC1 and alters the MUC2:MUC5AC ratio; Fut8-/- mice exhibit thinner proximal colon mucus with altered neutral-to-acidic mucin ratio. |
FUT8 overexpression and KD in HT29-18N2 cells, MUC1 cell-surface localization, mucin secretion assay, Fut8-/- mouse mucus analysis |
PNAS |
High |
36252012
|
| 2021 |
FUT8 activity is directed by glycan structure and protein context: complex-type N-glycans are the preferred substrates in cells; peptide/protein context expands FUT8 activity to high-mannose and paucimannose N-glycans; sialylation of N-glycans significantly reduces FUT8 substrate efficiency. |
In vitro FUT8 assay with N-glycan library, N-glycopeptides, STD NMR, CHO cell glycan engineering (KO of specific glycosylation enzymes), mass spectrometry glycan analysis |
ACS catalysis |
High |
35662980
|
| 2021 |
FUT8 modifies core fucosylation levels on TNF receptors (TNFRs); lower TNFR fucosylation in osteosarcoma cells activates the non-canonical NF-κB signaling pathway and decreases mitochondria-dependent apoptosis, promoting OS cell survival. |
FUT8 expression analysis in OS cell lines, gain/loss-of-function, TNFR fucosylation analysis, non-canonical NF-κB pathway assay, apoptosis assay |
Cell death & disease |
Medium |
34857735
|
| 2022 |
FUT8 stem region (two α-helices) is essential for FUT8 oligomerization/multimer formation but not for catalytic activity; the first helix of the stem region is critical for multimer formation; loss of the stem region destabilizes FUT8 protein, increases ER localization, and shortens its half-life. |
FUT8Δstem mutants expressed in FUT8-KO HEK293 cells, immunoprecipitation, native-PAGE, ER localization analysis, protein half-life assay |
Journal of biological chemistry |
High |
36336076
|
| 2022 |
Quantitative glycoproteomics identifies 140 common core-fucosylated FUT8 target glycoproteins in invasive breast cancer cells; core fucosylation of integrin αvβ5 is crucial for breast cancer cell adhesion to vitronectin; core fucosylation of IL6ST is crucial for enhanced cellular signaling by IL-6 and oncostatin M. |
Quantitative glycoproteomics on FUT8-KO vs. wild-type cells, LCA blot, LC-MS/MS validation, functional adhesion assays, ingenuity pathway analysis |
Breast cancer research : BCR |
High |
35303925
|
| 2022 |
FUT8 interacts with galectin-3 (Gal-3) by co-immunoprecipitation; FUT8 knockdown downregulates Gal-3 expression and inhibits FAK/Akt signaling, thereby suppressing TGF-β1-induced fibroblast proliferation, migration, and fibrosis; overexpression of Gal-3 reverses the effects of FUT8 silencing. |
Co-IP assay, siRNA knockdown in MRC-5 cells, rescue with Gal-3 overexpression, CCK-8/BrdU/wound healing assays, western blot, bleomycin mouse model |
Journal of Southern Medical University |
Medium |
36073215
|
| 2023 |
FUT8-silence-induced defucosylation at N104 on B7-H3 in colorectal cancer cells exposes a 106-110 SLRLQ motif recognized by HSC70 (HSPA8), which then drives lysosomal degradation of B7-H3 via the chaperone-mediated autophagy (CMA) pathway; the FUT8 inhibitor FDW028 recapitulates this mechanism. |
FUT8 siRNA, mass spectrometry identification of HSPA8 binding, CMA pathway assay with LAMP2A, in vivo CRC pulmonary metastasis model with FDW028 |
Cell death & disease |
High |
37537172
|
| 2023 |
FUT8-catalyzed core fucosylation is required for AβO-induced pro-inflammatory microglial activation; FUT8 inhibition (siRNA or pharmacological) reduces pro-inflammatory cytokines and p38MAPK activation in AβO-stimulated hiMG; p53 binds to the Fut8 promoter and is required for FUT8 overexpression in AβO-activated microglia. |
Human iPSC-derived microglia model, siRNA knockdown, cytokine assays, p38MAPK western blot, p53 promoter binding analysis, p53 siRNA rescue |
Glia |
Medium |
36692036
|
| 2023 |
FUT8 directly catalyzes core fucosylation of SEMA7A at five N-linked glycosylation sites (Asn 105, 157, 258, 330, 602) via a direct protein-protein interaction; this glycosylation is required for SEMA7A trafficking from cytoplasm to cell membrane; EGF increases SEMA7A-FUT8 binding affinity; glycosylated SEMA7A drives CD8+ T cell exhaustion and defines RBM4 as downstream effector of PD-L1 alternative splicing. |
Co-IP, MS identification of glycosylation sites, trafficking/localization assay, EGF stimulation, T cell exhaustion assay, RBM4/PD-L1 functional analysis |
International journal of oral science |
Medium |
38548747
|
| 2023 |
FUT8-mediated core fucosylation of VEGFR-2 activates the AKT pathway in pulmonary artery smooth muscle cells; FUT8 knockdown inhibits PDGF-BB-induced PASMC proliferation, migration, phenotypic switching, and apoptosis resistance; AKT activator SC79 partially reverses siFUT8 effects. |
siRNA knockdown in PASMCs, AKT pathway western blot, cell proliferation/migration/apoptosis assays, monocrotaline PAH rat model with 2FF inhibitor |
Aging and disease |
Medium |
37196106
|
| 2023 |
Loss of FUT8 in renal tubular epithelial cells ameliorates IRI-induced renal inflammation-to-fibrosis transition via the TLR3 core fucosylation-NF-κB signaling pathway; tubular epithelial cell-specific FUT8 knockout mouse demonstrates cell type-specific role. |
TEC-specific conditional FUT8 knockout mouse, IRI model, TLR3 core fucosylation analysis, NF-κB signaling assay |
FASEB journal |
High |
37432656
|
| 2024 |
FUT8 interacts with TMEM67, a ciliary transition zone component, and catalyzes its core fucosylation; core fucosylation stabilizes TMEM67 by preventing its autophagy-mediated degradation and ensures its proper localization to the transition zone for ciliogenesis; Fut8-deficient mice exhibit ciliary defects in kidney, brain, and trachea; ectopic Cntn2 (core fucosylation target) rescues neuronal defects from Fut8 deficiency. |
Mass spectrometry proteomics, Co-IP of FUT8-TMEM67, core fucosylation assay, autophagy degradation assay, TMEM67 localization, Fut8 conditional KO mouse with organ-specific ciliary phenotyping |
Journal of cell biology |
High |
40728580
|
| 2024 |
FUT8 inhibitor development: GDP binding induces a closed, catalytically competent active site via conformational rearrangement of two flexible loops; a selective small-molecule inhibitor (KD = 49 nM) binds only in the presence of GDP, generating a reactive naphthoquinone methide that covalently reacts with FUT8; prodrug derivatization enables cellular suppression of EGFR and T-cell signaling. |
High-throughput screening, SPR binding, mechanistic inhibitor studies, cell-based core fucose assay, EGFR/T-cell signaling assays |
Angewandte Chemie |
High |
39340265
|
| 2025 |
FUT8 catalysis proceeds via a GDP-fucose-induced concerted loop closure creating a competent active site; the reaction follows a highly asynchronous SN2 inverting mechanism involving cleavage of the fucose-GDP glycosidic bond, formation of the new glycosidic bond, and H-transfer to the catalytic Glu373 as three stages with a transient intimate ion pair (lifetime 350–800 fs); no stable oxocarbenium intermediate forms. |
Molecular dynamics, QM/MM simulations, metadynamics, electron localization function (ELF) topological analysis |
ACS catalysis |
Medium |
41743314
|
| 2011 |
Increased FUT8 expression and activity in the liver are strongly linked to age-related increases in core-fucosylated N-glycans; age-related increased FUT8 activity influences IGF-1R signaling sensitivity. |
N-glycan profiling of mouse serum in different age groups, C57BL/6 mice including klotho-deficient and Snell Dwarf mice, caloric restriction model, FUT8 expression and activity measurement in liver |
Aging cell |
Medium |
21951615
|
| 2018 |
Biallelic loss-of-function mutations in human FUT8 cause a congenital disorder of glycosylation (FUT8-CDG) characterized by complete absence of FUT8 protein and substantial deficiency of core-fucosylated N-glycans in fibroblasts and serum, causing intrauterine growth retardation, developmental delays, neurological impairments, and respiratory complications. |
Whole-exome sequencing, functional studies in patient-derived primary fibroblasts, N-glycan analysis by mass spectrometry, splicing analysis |
American journal of human genetics |
High |
29304374
|
| 2020 |
FUT8 knockout in CHO cells alters not only core fucosylation but broadly changes other glycosylation processes; sialyltransferases and glucosyltransferases are sharply decreased in FUT8KO cells; 28.6% of 442 identified glycoproteins show significantly altered expression, revealing FUT8's broad impact on the glycosylation machinery. |
FUT8 KO CHO cells, large-scale glycoproteomics with HILIC enrichment, high-resolution LC-MS, SILAC-based proteomics |
Frontiers in chemistry |
Medium |
34778211
|
| 2025 |
FUT8 interacts with TGEV nonstructural proteins NSP3 and NSP4 (independent of its fucosyltransferase enzymatic activity) to facilitate formation of double-membrane vesicles (DMVs) required for viral replication; FUT8 enzymatic inhibitor FDW028 had no effect, confirming this role is non-enzymatic. |
Genome-wide CRISPR/Cas9 screen, FUT8 KO characterization, viral internalization and replication assays, DMV formation assay, Co-IP with NSP3/NSP4, FDW028 enzymatic inhibitor comparison |
International journal of biological macromolecules |
Medium |
41205942
|
| 2025 |
FUT8 promotes core fucosylation of CD36 in pericytes, increasing CD36 expression and activating the mitochondrial-dependent apoptosis signaling pathway, thereby driving pericyte-to-myofibroblast transition and AKI-to-CKD progression. |
GEO/DISCO database analysis, IRI mouse model, hypoxia/reoxygenation pericyte model, IP/confocal-IF for CD36 CF, flow cytometry apoptosis, JC-1 mitochondrial membrane potential assay |
Molecular medicine |
Medium |
39563263
|
| 2025 |
FUT8 promotes PKM2 K115 lactylation by enhancing HIF-1α-driven glycolysis and lactate production in clear cell RCC; increased PKM2 lactylation boosts PKM2 enzymatic activity while reducing its nuclear localization, driving EMT and malignant progression. |
FUT8 knockdown in ccRCC cells and xenografts, HIF-1α-glycolysis assay, lactylation mass spectrometry, PKM2 activity assay, nuclear/cytoplasmic fractionation |
Cell death discovery |
Medium |
41857011
|
| 2025 |
FUT8-mediated core fucosylation of NCEH1 stabilizes NCEH1 by preventing proteasomal degradation; core-fucosylated NCEH1 facilitates LPA secretion, driving M2-like tumor-associated macrophage polarization and promoting HGSC peritoneal metastasis. |
Glycoproteomic assay identifying NCEH1 as core fucosylation substrate, proteasomal degradation assay, non-targeted metabolomics for LPA, macrophage polarization assay, in vitro and in vivo metastasis models |
Oncogene |
Medium |
41786877
|
| 2025 |
FUT8 upregulates Unc5b core fucosylation (primarily in the ER), which activates the p-CDC42/p-PAK pathway and reduces macrophage migration capacity, thereby promoting foam cell retention and atherosclerosis progression; defucosylation of Unc5b rescues macrophage migration. |
IP assay for Fut8-Unc5b core fucosylation, genetic deletion of fucosylation sites, ApoE-/- mouse model, Unc5b KD/overexpression, p-CDC42/p-PAK western blot, wound healing migration assay |
Cell & bioscience |
Medium |
36670464
|
| 2025 |
FUT8 promotes core fucosylation of Toll-like receptor 4 (TLR4) in gingival fibroblasts, enhancing NF-κB signaling sensitivity and inflammatory cytokine secretion; dual-gene silencing of Fut8 and TLR4 confirms their synergistic role in the inflammatory cascade; core fucosylation inhibitor 2FF alleviates periodontitis in a mouse model. |
Co-immunoprecipitation, TLR4 glycosylation assay, gene silencing, NF-κB pathway analysis, cytokine assay, periodontitis mouse model with 2FF |
International dental journal |
Medium |
41653834
|
| 2025 |
FUT8 depletion reduces cAMP production following FSH stimulation in granulosa cells, impairing FSHR signaling; Fut8-/- mouse oocytes exhibit abnormal zona pellucida formation and impaired embryonic development; FIGLA expression and other embryonic development genes are downregulated in Fut8-/- ovaries. |
FUT8 knockdown in KGN cells, cAMP assay, Fut8-/- mouse oocyte/embryo analysis, zona pellucida imaging, FIGLA expression analysis |
Journal of assisted reproduction and genetics |
Medium |
40473957
|
| 2025 |
FUT8 promotes HDM-induced epithelial-mesenchymal transition and IL-25/IL-33 inflammatory responses in bronchial epithelial cells by catalyzing core fucosylation of GLUT1 at Asn45 (N45), stabilizing GLUT1 protein and enhancing glycolysis; the GLUT1 N45Q mutant abolishes this effect. |
Lectin pull-down assay for GLUT1-FUT8 interaction, FUT8 overexpression/silencing, GLUT1 half-life assay, N45Q mutagenesis rescue, ECAR/ATP/lactate assays, IL-25/IL-33 secretion assay |
Biochemical and biophysical research communications |
High |
41027183
|