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malfunction
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In an analysis of microarray data of in a large cohort of 1681 breast tumors, there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression, especially in tumors with a positive estrogen receptor (ER) status.
malfunction
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inhibiting UDP-glucose ceramide glycosyltransferase increases the susceptibility of p53-deficient cells, but not p53-expressing cells, to mitomycin C. Enzyme down-regulation contributes to the accumulation of ceramide in cells lacking p53
malfunction
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reduced enzyme expression in the fat body causes a reduction of fat storage
malfunction
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silencing glucosylceramide synthase expression disrupts Gb3 synthesis and selectively kills breast cancer stem cells through deactivation of c-Src/beta-catenin signaling
malfunction
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when each gene function is disrupted, the brood size of the animal markedly decreases and abnormal oocytes and multinucleated embryos are formed. Knockdown of the germline expression of gene cgt-3 results in abnormal oocyte formation and abnormal embryonic cell division
malfunction
enzyme inhibitors affect the expression of lactosylceramide, neolacto, ganglio, and globo series glycosphingolipids in a panel of human cancer cell lines. Their cell-surface glycosphingolipid expression considerably varies among cell lines and sublethal concentrations (IC10) of both inhibitors preferentially and significantly reduce the expression of globo Gb3 glycosphingolipids in the cancer cell lines IGROV1, BG1, HT29 and T47D, whereas globo SSEA3 glycosphingolipid expression is only reduced in BG1 cells. The neolacto and ganglio glycosphingolipid series is not affected. Lactosylceramider, the precursor of all GlcCer-related glycosphingolipids, is significantly reduced only in BG1 cells treated with DL-threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, overview
malfunction
genetically silencing the enzyme induces apoptosis with induced ceramide accumulation, accompanied by a decrease in glucosylceramide, and inhibits Bcl-xL function. Simultaneous GCS inhibition and VNR treatment causes a decrease in Bcl-xL expression. Pharmacologically inhibiting enzyme GCS induces ceramide accumulation in vinorelbine-treated A549 and AS2 cells
malfunction
substrate reduction therapy by selectively inhibiting glucosylceramide synthase is used in treatment of Fabry disease, an X-linked inherited glycosphingolipid storage disorder, that is caused by the deficient activity of alpha-galactosidase A, which results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid), leading to kidney, heart, and cerebrovascular disease. Kidneys of both Fabry and wild-type mice treated with enzyme inhibitor GCS Genz-682452 show reductions of galactosylceramide (about 85%) and digalactosylceramide (about 60%), a combination therapy with Genz-682452 and alpha-galactosidase A is more efficacious than either therapy alone at reducing glycosphingolipid levels in Fabry mice, phenotype, overview
malfunction
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substrate reduction therapy by selectively inhibiting glucosylceramide synthase is used in treatment of Fabry disease, an X-linked inherited glycosphingolipid storage disorder, that is caused by the deficient activity of alpha-galactosidase A, which results in the lysosomal accumulation in various cell types of its glycolipid substrates, including globotriaosylceramide and lysoglobotriaosylceramide (globotriaosyl lysosphingolipid), leading to kidney, heart, and cerebrovascular disease. Kidneys of both Fabry and wild-type mice treated with enzyme inhibitor GCS Genz-682452 show reductions of galactosylceramide (about 85%) and digalactosylceramide (about 60%), a combination therapy with Genz-682452 and alpha-galactosidase A is more efficacious than either therapy alone at reducing glycosphingolipid levels in Fabry mice, phenotype, overview
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metabolism
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key enzyme for the synthesis of glycosphingolipids which plays a role in physiology and diseases for instance in drug-resistant cancers
metabolism
glucosylceramide synthase catalyzes the first committed step in the biosynthesis of glucosylceramide-related glycosphingolipids, pathway overview
physiological function
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glucosylceramide synthase expression in the fat body regulates energy metabolism in Drosophila melanogaster
physiological function
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the Ugcg gene is indispensable in the gremlin in oocyte formation and early embryonic division
physiological function
an increase in glucosylceramide synthase induces Bcl-xL-mediated cell survival in vinorelbine-resistant lung adenocarcinoma cells, potential mechanism of glucosylceramide synthase-mediated Vinca alkaloid vinorelbine resistance in human lung adenocarcinoma cells, overview
physiological function
the enzyme catalyzes the transfer of glucose from UDP-glucose to ceramide to form glucosylceramide
physiological function
UGCG overexpression in breast cancer cells leads to morphological changes, which enhance proliferation and doxorubicin resistance. These effects seem to be mediated by an altered composition of glycosphingolipid-enriched microdomains, especially an accumulation of globotriaosylceramide and glucosylceramide, which leads to an activation of Akt and ERK1/2. The induction of the Akt and ERK1/2 signaling pathway results in an increased gene expression of multidrug resistance protein 1 and anti-apoptotic genes and a decrease of pro-apoptotic gene expression
additional information
the use of ethyl-2-amino-6-bromo-(1-cyano-2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate, i.e. HA14-1, as a Bcl-2 inhibitor in studies of apoptosis might produce misleading results, because HA14-1 can also affect a ceramide-mediated cell death pathway by inhibiting GlcT-1. Bcl-2 is a protein factor known to suppress apoptosis by binding and inactivating pro-apoptotic proteins such as Bax and BH3-only family proteins
additional information
vinorelbine works as an anticancer agent by inducing cell growth inhibition and cell apoptosis