| 2007 |
GMDS (GDP-mannose 4,6-dehydratase) encodes the first enzyme in the de novo GDP-fucose biosynthesis pathway; siRNA-mediated knockdown of GMDS in CHO cells reduced cellular fucosylation in a manner correlated with mRNA expression levels, and GMDS knockout cells were devoid of intracellular GDP-fucose and produced completely non-fucosylated antibodies, confirming GMDS is the rate-limiting enzyme in the de novo GDP-fucose synthesis pathway with no functional redundancy. |
siRNA knockdown, GMDS knockout cell line generation, GDP-fucose quantification by HPLC, antibody fucosylation analysis |
Journal of biotechnology |
High |
17559959 18047682
|
| 2007 |
Simultaneous double knockdown of GMDS and FUT8 (alpha-1,6-fucosyltransferase) produced a synergistic effect on reduction of antibody fucosylation, achieving complete defucosylation, whereas knockdown of GMDS combined with GDP-fucose transporter (GFT) siRNA did not show the same synergistic effect, indicating that GMDS and FUT8 collaborate in the same intracellular fucosylation process. |
siRNA double knockdown, flow cytometry for fucosylation, ADCC assay |
BMC biotechnology |
Medium |
18047682
|
| 2009 |
Loss-of-function mutations in GMDS in the human colon cancer cell line HCT116 result in virtually complete loss of cellular fucosylation; re-introduction of wild-type GMDS restored cellular fucosylation. GMDS-deficient cells were resistant to TRAIL-induced apoptosis, and GMDS-rescued cells transplanted into athymic mice showed dramatically suppressed tumor growth and metastasis through NK cell-mediated tumor surveillance. Anti-TRAIL blocking antibody suppressed the accelerated direct cell lysis of GMDS-rescued cells by splenocytes, placing GMDS upstream of TRAIL signaling in NK cell-mediated tumor immune surveillance. |
Mutational analysis, GMDS transfection/rescue, in vitro TRAIL apoptosis assay, xenograft mouse model, NK cell cytotoxicity assay, anti-TRAIL blocking antibody |
Gastroenterology |
High |
19361506
|
| 2011 |
GMDS deficiency inhibits both DR4- and DR5-mediated (and CD95-mediated) apoptosis, but not intrinsic (drug-induced) apoptosis. Mechanistically, GMDS deficiency does not block primary DISC formation or caspase-8 recruitment/activation at the DISC, but specifically inhibits formation of the secondary FADD-dependent complex II (comprising caspase-8 and cFLIP) downstream of DISC. DR4 was found to be fucosylated while DR5 was not, yet GMDS deficiency blocked both pathways, indicating the block occurs independent of direct fucosylation of death receptors at the level of complex II assembly. |
Co-immunoprecipitation of DISC components, caspase-8 activity assay, western blot for complex II components, comparison of DR4/DR5 fucosylation status |
The Journal of biological chemistry |
High |
22027835
|
| 2011 |
In Drosophila, GMD (the ortholog of human GMDS) activity regulates the stability of the Notch protein; low GMD expression leads to Notch degradation that is entirely dependent on OFUT1 (O-fucosyltransferase-1). The GDP-fucose/OFUT1 balance determines OFUT1's ability to endocytose and degrade Notch, placing GMD upstream of OFUT1-mediated Notch protein stability. |
Drosophila genetics (mutant analysis, UAS/Gal4 system), epistasis analysis with OFUT1 and Notch Abruptex mutants |
Biological research |
Medium |
21720678
|
| 2018 |
GMDS knockdown in human lung adenocarcinoma cells (A549 and H1299) impaired cell proliferation, colony formation, induced cell cycle arrest and apoptosis in vitro, and inhibited tumorigenesis in a xenograft mouse model. Transcriptome analysis identified the CASP8-CDKN1A axis as potentially critical, consistent with GMDS acting upstream of apoptotic signaling in this cancer context. |
Lentiviral shRNA knockdown, cell viability/proliferation assays, flow cytometry (cell cycle and apoptosis), xenograft mouse model, microarray transcriptome analysis |
BMC cancer |
Medium |
29843634
|
| 2025 |
A point mutation in mouse Gmds (ENU-induced) caused a near-complete block in T cell development at the double-positive stage in the thymus, with a cell-intrinsic requirement demonstrated by bone marrow reconstitution and mixed chimera experiments showing Gmds-deficient T cells could not compete from the DP stage onward, while B cell subsets were broadly normal. |
ENU mutagenesis mouse model, flow cytometry immunophenotyping, bone marrow reconstitution (Rag1 mice), mixed chimera experiments |
Frontiers in immunology |
High |
40642090
|
| 2025 |
Loss of gmds function in zebrafish increased hair cell number in neuromasts and accelerated hair cell regeneration after neomycin-induced ablation. Pharmacological inhibition of Notch signaling enhanced hair cell regeneration in wild-type siblings but less so in gmds mutants, indicating that Notch signaling acts partially downstream of gmds in regulating hair cell regeneration. |
CRISPR/Cas9 gmds mutant zebrafish, neomycin hair cell ablation assay, pharmacological Notch inhibition, live imaging of hair cell regeneration |
International journal of molecular sciences |
Medium |
41097001
|
| 2025 |
gmds haploinsufficiency in zebrafish (CRISPR/Cas9) caused retinal ganglion cell (RGC) layer thinning, RGC loss, and reduced optic nerve head width. RNA-seq showed significant downregulation of stress response genes (including crystallin family) and increased expression of cell death genes in gmds heterozygous mutant eyes, suggesting GMDS regulates ocular stress responses and RGC survival. |
CRISPR/Cas9 zebrafish mutant, RNAseq transcriptome analysis, histological/morphological phenotyping of eye |
Experimental eye research |
Medium |
40571142
|