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arachidoyl-CoA + dihydrosphingosine
N-(arachidoyl)-dihydrosphingosine + CoA
-
-
-
-
?
D-erythro-sphinganine + stearoyl-CoA
N-stearoyl-D-sphinganine + CoA
dihydrosphingosine + 2-hydroxystearoyl-CoA
N-2-hydroxystearoylsphingosine + CoA
-
-
-
?
dihydrosphingosine + palmitoyl-CoA
N-palmitoyldihydrosphingosine + CoA
low activity
-
-
?
dihydrosphingosine + stearoyl-CoA
N-stearoyldihydrosphingosine + CoA
oleoyl-CoA + dihydrosphingosine
N-(oleoyl)-dihydrosphingosine + CoA
-
-
-
-
?
oleoyl-CoA + sphingolipid
N-(oleoyl)-sphingolipid + CoA
-
-
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
stearoyl-CoA + a sphingoid base
an N-(stearoyl)-sphingoid base + CoA
stearoyl-CoA + dihydroceramide
N-(stearoyl)-dihydroceramide + CoA
-
-
-
-
?
stearoyl-CoA + dihydrosphingosine
CoA + N-stearoyldihydrosphingosine
-
-
-
-
?
stearoyl-CoA + dihydrosphingosine
N-(stearoyl)-dihydrosphingosine + CoA
-
-
-
-
?
stearoyl-CoA + NBD-dihydrosphingosine
N-(stearoyl)-NBD-dihydroceramide + CoA
-
-
-
-
?
stearoyl-CoA + NBD-labelled sphinganine
N-(stearoyl)-sphinganine + CoA
-
NBD-labelled sphinganine is (2S,3R)-2-amino-18-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)octadecane-1,3-diol
-
-
?
stearoyl-CoA + sphinganine
N-(stearoyl)-sphinganine + CoA
additional information
?
-
D-erythro-sphinganine + stearoyl-CoA
N-stearoyl-D-sphinganine + CoA
-
-
-
-
?
D-erythro-sphinganine + stearoyl-CoA
N-stearoyl-D-sphinganine + CoA
-
-
-
-
?
dihydrosphingosine + stearoyl-CoA
N-stearoyldihydrosphingosine + CoA
-
-
-
?
dihydrosphingosine + stearoyl-CoA
N-stearoyldihydrosphingosine + CoA
highly preferred substrate
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
-
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
-
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
-
-
-
-
?
stearoyl-CoA + a sphingoid base
an N-(stearoyl)-sphingoid base + CoA
-
-
-
-
?
stearoyl-CoA + a sphingoid base
an N-(stearoyl)-sphingoid base + CoA
-
-
-
-
?
stearoyl-CoA + sphinganine
N-(stearoyl)-sphinganine + CoA
-
-
-
?
stearoyl-CoA + sphinganine
N-(stearoyl)-sphinganine + CoA
-
-
-
?
additional information
?
-
CERS1 preferentially catalyzes the transfer of a C18:0 fatty acid, forming C18:0 dihydroceramide (d18:0/18:0 ceramide)
-
-
?
additional information
?
-
clear preference for the C18:0 NBD-dihydroceramide synthesis is observed with extracts of human frontal cortex grey matter
-
-
?
additional information
?
-
CERS activity is assayed using LC-MS/MS for product quantification, crude extracts containing cell membranes are firstly prepared from tissues or cultured cells, reactions contain deuterated dihydrosphingosine (or sphingosine) and a fatty acid substrate linked to CoA (C16:0 to C24:0/24:1), detailed method descritpion and evaluation, overview
-
-
?
additional information
?
-
CERS1-expressing HEK293 cell extracts show a clear preference for utilisation of the C18:0 fatty acid substrate when presented with equimolar concentrations of C16:0, C18:0, C24:0, and C24:1 fatty acid substrates. CERS1 preferentially catalyses the addition of 18-carbon (C18:0) fatty acids to dihydrosphingosine. No activity with lignoceroyl-CA, and poor activity with nervonoyl-CoA. Improvement of a fluorescent assay, using HPLC using C16:0, C18:0, and C24:1 fatty acids and commercially available sphinganine-NBD, i.e. 7-nitro-2-1,3-benzoxadiazole-labelled dihydrosphingosine or (2S,3R)-2-amino-18((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)octadecane-1-3-diol, as substrates, very accurate and sensitive method for quantification of CERS activity, method evaluation
-
-
?
additional information
?
-
substrate specificity, overview. CerS1 can use C18:0-CoA but not C18:1-CoA as a substrate
-
-
?
additional information
?
-
C18:0 fatty acid CoA, but not cis-C18:1 fatty acid CoAs, are substrates for LASS1
-
-
?
additional information
?
-
-
C18:0 fatty acid CoA, but not cis-C18:1 fatty acid CoAs, are substrates for LASS1
-
-
?
additional information
?
-
C18:0-CoA is the best substrate for Lass1-dependent ceramide synthesis. C18:1-CoA, which has the same chain length as C18:0, is not a good substrate at all. Recombinant Lass1 produces preferentially C18:0-ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
-
C18:0-CoA is the best substrate for Lass1-dependent ceramide synthesis. C18:1-CoA, which has the same chain length as C18:0, is not a good substrate at all. Recombinant Lass1 produces preferentially C18:0-ceramides in transgenic HEK-293T cells
-
-
?
additional information
?
-
no activity with palmitoyl-CoA
-
-
-
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dihydrosphingosine + 2-hydroxystearoyl-CoA
N-2-hydroxystearoylsphingosine + CoA
-
-
-
?
dihydrosphingosine + palmitoyl-CoA
N-palmitoyldihydrosphingosine + CoA
low activity
-
-
?
dihydrosphingosine + stearoyl-CoA
N-stearoyldihydrosphingosine + CoA
oleoyl-CoA + sphingolipid
N-(oleoyl)-sphingolipid + CoA
-
-
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
stearoyl-CoA + a sphingoid base
an N-(stearoyl)-sphingoid base + CoA
stearoyl-CoA + dihydroceramide
N-(stearoyl)-dihydroceramide + CoA
-
-
-
-
?
stearoyl-CoA + dihydrosphingosine
CoA + N-stearoyldihydrosphingosine
-
-
-
-
?
stearoyl-CoA + NBD-labelled sphinganine
N-(stearoyl)-sphinganine + CoA
-
NBD-labelled sphinganine is (2S,3R)-2-amino-18-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)octadecane-1,3-diol
-
-
?
stearoyl-CoA + sphinganine
N-(stearoyl)-sphinganine + CoA
-
-
-
?
additional information
?
-
dihydrosphingosine + stearoyl-CoA
N-stearoyldihydrosphingosine + CoA
-
-
-
?
dihydrosphingosine + stearoyl-CoA
N-stearoyldihydrosphingosine + CoA
highly preferred substrate
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
-
-
-
?
sphinganine + stearoyl-CoA
N-stearoylsphinganine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
-
-
-
?
sphingosine + stearoyl-CoA
N-stearoylsphingosine + CoA
-
-
-
-
?
stearoyl-CoA + a sphingoid base
an N-(stearoyl)-sphingoid base + CoA
-
-
-
-
?
stearoyl-CoA + a sphingoid base
an N-(stearoyl)-sphingoid base + CoA
-
-
-
-
?
additional information
?
-
CERS1 preferentially catalyzes the transfer of a C18:0 fatty acid, forming C18:0 dihydroceramide (d18:0/18:0 ceramide)
-
-
?
additional information
?
-
clear preference for the C18:0 NBD-dihydroceramide synthesis is observed with extracts of human frontal cortex grey matter
-
-
?
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(1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol
-
FTY720
inhibits ceramide synthases and upregulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells. FTY720 is a sphingosine analogue and in clinical trials as an immunomodulator. Multifaceted mode of interaction between FTY720 and CerS. FTY720 inhibits ceramide synthesis using C18-CoA to a greater extent than other acyl-CoAs, dependence on acyl-CoA chain length of inhibition of CerS activity by FTY720. Sphinganine first binds to CerS to form an E-S (CerS-sphinganine) complex, and only after formation of this complex can FTY720 bind. The binding sites of FTY720 and acyl-CoA appear to be distinct, but the interaction between sphinganine binding and FTY720 binding nevertheless impacts the rate of the reaction with respect to acyl-CoA. FTY720 inhibits ceramide synthesis at high sphinganine concentrations in vivo, but not at low concentrations, supporting a complex, possibly allosteric mode of interaction between sphinganine and FTY720 and is consistent with uncompetitive inhibitors being most effective at high substrate concentrations. FTY720 acts as a noncompetitive inhibitor toward C18-CoA. The inhibition of FTY720 toward C18-CoA is allosteric under the normal reaction conditions. Sphingolipid composition of HEK cells treated with FTY720, overview
FTY720
-
competitive inhibitor
fumonisin B1
-
fumonisin B1
inhibits the increase in total cellular ceramide induced by UV-C irradiation
fumonisin B1
-
reversible competitive inhibition, inhibits ceramide synthase in mouse brain microsomes with a competitive-like kinetic behavior with respect to both sphinganine and stearoyl-CoA. Fumonisin B1 inhibits ceramide synthase activity when palmitoyl-CoA, stearoyl-CoA, or lignoceroyl-CoA are used as the co-substrate, cf. EC 2.3.1.297 and 2.3.1.24
fumonisin B1
an in vitro inhibitor of (dihydro)-ceramide synthase, inhibits wild-type and mutant enzymes in vivo in HeLa cells
additional information
in contrast to the dual effects of fumonisin B1, which is only observed in cells overexpressing CerS, FTY720 elevates ceramide levels in untransfected cells
-
additional information
-
fumonisins block sphingosine biosynthesis by inhibiting the conversion of sphinganine to dihydroceramides, which precedes introduction of the 4,5-trans-double bond of sphingosine. Fumonisins, mycotoxins produced by Fusarium moniliforme and a number of other fungi, cause neuronal degeneration, liver and renal toxicity, cancer, and other injury to animals. Fumonisin Bl inhibits complex sphirqolipid synthesis from galactose and sphinganine, effects on the amounts of free sphingosine and sphinganine and on total complex sphingolipids, overview
-
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Adenocarcinoma of Lung
Mechanisms of ceramide-mediated repression of the human telomerase reverse transcriptase promoter via deacetylation of Sp3 by histone deacetylase 1.
Ataxia
Progressive Myoclonic Epilepsy Type 8 Due to CERS1 Deficiency: A Novel Mutation with Prominent Ataxia.
Carcinoma
Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress.
Carcinoma
Increased killing of SCCVII squamous cell carcinoma cells after the combination of Pc 4 photodynamic therapy and dasatinib is associated with enhanced caspase-3 activity and ceramide synthase 1 upregulation.
Carcinoma, Squamous Cell
Increased killing of SCCVII squamous cell carcinoma cells after the combination of Pc 4 photodynamic therapy and dasatinib is associated with enhanced caspase-3 activity and ceramide synthase 1 upregulation.
Carcinoma, Squamous Cell
siRNA-mediated down-regulation of ceramide synthase 1 leads to apoptotic resistance in human head and neck squamous carcinoma cells after photodynamic therapy.
Dementia
Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency.
Epilepsies, Myoclonic
Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency.
Glioblastoma
Autophagy activation, lipotoxicity and lysosomal membrane permeabilization synergize to promote pimozide- and loperamide-induced glioma cell death.
Glioma
Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma.
Head and Neck Neoplasms
Diverse functions of ceramide in cancer cell death and proliferation.
Heart Failure
A tissue-specific screen of ceramide expression in aged mice identifies ceramide synthase-1 and ceramide synthase-5 as potential regulators of fiber size and strength in skeletal muscle.
Inflammatory Bowel Diseases
mTNF reverse signalling induced by TNF? antagonists involves a GDF-1 dependent pathway: implications for Crohn's disease.
Insulin Resistance
A selective inhibitor of ceramide synthase 1 reveals a novel role in fat metabolism.
Insulin Resistance
Impact of insulin deprivation and treatment on sphingolipid distribution in different muscle subcellular compartments of streptozotocin-diabetic C57Bl/6 mice.
Mouth Neoplasms
Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress.
Myoclonic Epilepsies, Progressive
Progressive Myoclonic Epilepsy Type 8 Due to CERS1 Deficiency: A Novel Mutation with Prominent Ataxia.
Neoplasm Metastasis
Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells.
Neoplasms
Ceramide targets autophagosomes to mitochondria and induces lethal mitophagy.
Neoplasms
Concerted functions of HDAC1 and microRNA-574-5p repress alternatively spliced ceramide synthase 1 expression in human cancer cells.
Neoplasms
Role of human longevity assurance gene 1 and C18-ceramide in chemotherapy-induced cell death in human head and neck squamous cell carcinomas.
Neoplasms
Stress-induced ER to Golgi translocation of ceramide synthase 1 is dependent on proteasomal processing.
Neoplasms
The Potential Role of CERS1 in Autophagy Through PI3K/AKT Signaling Pathway in Hypophysoma.
Neuroblastoma
Autosomal recessive progressive myoclonus epilepsy due to impaired ceramide synthesis.
sphingoid base n-stearoyltransferase deficiency
Ectopic expression of ceramide synthase 2 in neurons suppresses neurodegeneration induced by ceramide synthase 1 deficiency.
sphingoid base n-stearoyltransferase deficiency
Progressive Myoclonic Epilepsy Type 8 Due to CERS1 Deficiency: A Novel Mutation with Prominent Ataxia.
Squamous Cell Carcinoma of Head and Neck
Clinical relevance of ceramide metabolism in the pathogenesis of human head and neck squamous cell carcinoma (HNSCC): attenuation of C(18)-ceramide in HNSCC tumors correlates with lymphovascular invasion and nodal metastasis.
Squamous Cell Carcinoma of Head and Neck
Downregulation of ceramide synthase 1 promotes oral cancer through endoplasmic reticulum stress.
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evolution
Lag1 (longevity assurance gene 1) homologues, a family of transmembrane proteins found in all eukaryotes, is necessary for (dihydro)ceramide synthesis. All Lag1 homologues contain a highly conserved stretch of 52 amino acids known as the Lag1p motif, sequence comparisons, analysis of functional significance of the conserved Lag1p motif for (dihydro)ceramide synthesis, overview. The Lag1p motif is essential for the enzyme activity of all Lag1 homologues
evolution
Lass proteins are known to contain a TLC [TRAM/Lag1p/CLN8 (ceroid-lipofuscinoses, neuronal 8)] homology domain with the Lag1 motif. Lass family members Lass2, Lass4 and Lass5, but not Lass1, also contain a HOX (homeobox) domain
malfunction
inhibition of CerS is able to protect from cell death. Moreover, this protection occurs downstream or independently of mitochondrial permeabilization. Inhibition of CerS greatly inhibits plasma membrane permeabilization. Individual CerS knockdown does not significantly inhibit total ceramide accumulation. CerS1 knockdown has minimal effects in untreated cells and fails to prevent the accumulation of any Cer species following irradiation. Inhibition of CerS but not de novo synthesis inhibits plasma membrane rupture that is not specific to UV-C irradiation or MCF-7 cells
malfunction
profiles of non-hydroxylated and 2-hydroxy-ceramides in transgenic HeLa cells expressing different CerS isozymes and or different specific interfence RNAs, overview
malfunction
upon incubation of HEK cells with inhibitor FTY720, an increase in ceramide levels is observed, with no change in endogenous sphinganine levels. Similar increases are observed for hexosylceramide and sphingomyelin. Moreover, levels of C18-C22-ceramide are significantly increased, as are levels of C18-C22-hexosylceramide and C18-C22-sphingomyelin. This result is consistent with a complex mode of interaction of FTY720 with CerS, perhaps involving an allosteric element that is not preserved in vitro, whereby ceramide synthesis is stimulated in cells despite its inhibition by FTY720 in vitro
malfunction
-
enzyme deletion, and the consequent reduction of C18:0 acyl-chain ceramide specifically in skeletal muscle, enhances whole-body glucose metabolism in obesity through increased muscle-derived circulating Fgf21 protein concentrations. Enzyme deficiency protects from insulin resistance
malfunction
-
enzyme knockdown leads to inhibition of photodynamic therapy-induced caspase 3-like activation, of apoptosis and cell death. Enzyme knockdown is associated with global and selective decreases in ceramides and dihydroceramides, in particular C18-, C18:1- and C20-ceramide post-photodynamic therapy
metabolism
in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover
metabolism
in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover
metabolism
regulation of sphingolipid metabolism by UV-C irradiation, overview. Ceramide species that are the least abundant (e.g. C18-Cer, C18:1-Cer, C20-Cer, C22:1-Cer, etc.) exhibit the greatest fold increases. More abundant ceramide species (e.g. C16-Cer, C24-Cer, and C24:1-Cer) show more modest fold changes, although they account for much more of the overall increase in ceramides
metabolism
the N-(stearoyl)-sphinganine produced by the enzyme most significantly impacts neutral glycosphingolipid synthesis
physiological function
C18 ceramide synthesized by CERS1 is implicated in apoptosis and lethal autophagy
physiological function
ceramide synthase 1 (CerS1) is the most structurally and functionally distinct from the other CerS enzymes, the enzyme is regulated via a regulatory mechanism that specifically controls the level of CerS1 via ubiquitination and proteasome dependent protein turnover
physiological function
ceramide synthase 1 (CerS1) is the most structurally and functionally distinct from the other CerS enzymes, the enzyme is regulated via a regulatory mechanism that specifically controls the level of CerS1 via ubiquitination and proteasome dependent protein turnover
physiological function
ceramides are synthesized by ceramide synthases through the addition of a variable length fatty acid to the amine group of a sphingoid base. In mammalian cells, the sphingoid base used for de novo ceramide synthesis is usually the C18:0 lipid dihydrosphingosine. Ceramide synthesis is catalyzed by a family of six ceramide synthases (CERS1-6), each of which preferentially transfers fatty acids of different lengths to the amine group of dihydrosphingosine
physiological function
differences in the expression patterns of CerS family members may play an important role in the production of the CER/2-hydroxy ceramide (CER) compositions of different chain lengths observed in different cell types and even in the altered production that occurring during keratinocyte differentiation
physiological function
sphingolipid ceramides are widely implicated in the regulation of programmed cell death or apoptosis. CerS1 regulates C18:0-Cer synthesis
physiological function
-
enzyme overexpression in HEK-293 cells increases sensitivity to the chemotherapeutic agents cisplatin, carboplatin, doxorubicin and vincristine. The enzyme is a negative regulator of head and neck squamous cell carcinoma cells
physiological function
-
enzyme overexpression inhibits cell viability and induces cell death by activating endoplasmic reticulum stress, which induces lethal autophagy and inhibits PI3K/AKT signal pathway in U-251 and A-172 glioma cells. Enzyme overexpression also increases the sensitivity of U-251 and A-172 glioma cells to teniposide (VM-26)
physiological function
-
the enzyme regulates apoptotic resistance to photodynamic therapy for cancer treatment
additional information
the N-terminus is essential for catalytic activity
additional information
-
the N-terminus is essential for catalytic activity
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H182A/H183A
the mutant shows greatly reduced activity compared to the wild type enzyme
D210N
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
D213N
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
H182A/H183A
site-directed mutagenesis
H182D
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
H183D
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
H220D
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
K220L
site-directed mutagenesis, mutation in the Lag1p motif, the mutant enzyme is able to increase cellular C18 and C18:1 ceramide levels to a similar or slightly lesser extent than wild-type LASS1, the mutation does not affect the fatty acid chain-length specificity
L189E
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
L216E
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
L254E
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
L254M
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
S193A
site-directed mutagenesis, mutation in the Lag1p motif, the mutant enzyme is able to increase cellular C18 and C18:1 ceramide levels to a similar or slightly lesser extent than wild-type LASS1, mutation does not affect the fatty acid chain-length specificity
S231A
site-directed mutagenesis, mutation in the Lag1p motif, the mutant shows highly reduced activity, but the mutation does not affect its fatty acid chain-length specificity
additional information
-
in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. Recombinant isozyme CerS1 sensitizes cells to a wide range of drugs including cisplatin, carboplatin, doxorubicin and vincristine, in contrast to isozymes CerS4 and CerS5. The specific effect of CerS1 is mediated through the activation of the MAP kinase p38
additional information
in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, the turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. Recombinant isozyme CerS1 sensitizes cells to a wide range of drugs including cisplatin, carboplatin, doxorubicin and vincristine, in contrast to isozymes CerS4 and CerS5. The specific effect of CerS1 is mediated through the activation of the MAP kinase p38
additional information
profiles of non-hydroxylated and 2-hydroxy-ceramides in transgenic HeLa cells expressing different CerS isozymes and or different specific interfence RNAs, overview
additional information
in HEK-293 cells, both endogenous human CerS1 and ectopically expressed murine CerS1 have rapid basal turnover, CerS1 proteasomal degradation is ubiquitin mediated. The turnover requires CerS1 activity and is regulated by the opposing actions of p38 MAP kinase and protein kinase C (PKC), p38 MAP kinase is a positive regulator of turnover, while PKC is a negative regulator of turnover. Recombinantly expressed murine isozyme CerS1 sensitizes cells to a wide range of drugs including cisplatin, carboplatin, doxorubicin and vincristine, incontrast to isozymes CerS4 and CerS5. The specific effect of CerS1 is mediated through the activation of the MAP kinase p38
additional information
the some mutants shows altered specificity with substrates of different chain lengths, overview
additional information
-
the some mutants shows altered specificity with substrates of different chain lengths, overview
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DNA and amino acid sequence determination and analysis, sequence comparisons, phylogenetic tree, recombinant expression of HA-tagged enzyme in HEK-293T cells
expressed in HEK-293 cells
-
expressed in HEK-293T cells
gene CERS1, ectopic expression of N-terminally FLAG3-tagged CerS1 in HEK-293 or HeLa cells, recombinant expression of enzyme mutant H182A/H183A
gene CERS1, quantitative real-time PCR enzyme expression analysis
gene CERS1, recombinant expression in HEK-293 cells
gene CERS1, recombinant expression in HEK-293T cells, quantitative real-time quantitative PCR enzyme expression analysis
gene CERS1, recombinant overexpression in HEK cells, FTY720 inhibits CerS1 activity to a greater extent than CerS5 in the overexpressing cells
transient recombinant expression of N-terminally FLAG-tagged wild-type and mutant enzymes in HeLa cells, overexpression of wild-type LASS1 increases cellular levels of C18 and C18:1 ceramides by 10fold
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Mizutani, Y.; Kihara, A.; Igarashi, Y.
Mammalian Lass6 and its related family members regulate synthesis of specific ceramides
Biochem. J.
390
263-271
2005
Mus musculus (P27545), Mus musculus
brenda
Sridevi, P.; Alexander, H.; Laviad, E.L.; Pewzner-Jung, Y.; Hannink, M.; Futerman, A.H.; Alexander, S.
Ceramide synthase 1 is regulated by proteasomal mediated turnover
Biochim. Biophys. Acta
1793
1218-1227
2009
Homo sapiens, Homo sapiens (P27544), Mus musculus (P27545)
brenda
Narimatsu, S.; Soeda, S.; Tanaka, T.; Kishimoto, Y.
Solubilization and partial characterization of fatty acyl-CoA sphingosine acyltransferase (ceramide synthetase) from rat liver and brain
Biochim. Biophys. Acta
877
334-341
1986
Rattus norvegicus
brenda
Merrill, A.H.; van Echten, G.; Wang, E.; Sandhoff, K.
Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ
J. Biol. Chem.
268
27299-27306
1993
Mus musculus, Mus musculus NMRI
brenda
Spassieva, S.; Seo, J.G.; Jiang, J.C.; Bielawski, J.; Alvarez-Vasquez, F.; Jazwinski, S.M.; Hannun, Y.A.; Obeid, L.M.
Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity
J. Biol. Chem.
281
33931-33938
2006
Mus musculus (P27545), Mus musculus
brenda
Lahiri, S.; Park, H.; Laviad, E.L.; Lu, X.; Bittman, R.; Futerman, A.H.
Ceramide synthesis is modulated by the sphingosine analog FTY720 via a mixture of uncompetitive and noncompetitive inhibition in an Acyl-CoA chain length-dependent manner
J. Biol. Chem.
284
16090-16098
2009
Homo sapiens (P27544)
brenda
Mullen, T.D.; Jenkins, R.W.; Clarke, C.J.; Bielawski, J.; Hannun, Y.A.; Obeid, L.M.
Ceramide synthase-dependent ceramide generation and programmed cell death involvement of salvage pathway in regulating postmitochondrial events
J. Biol. Chem.
286
15929-15942
2011
Homo sapiens (P27544)
brenda
Mizutani, Y.; Kihara, A.; Chiba, H.; Tojo, H.; Igarashi, Y.
2-Hydroxy-ceramide synthesis by ceramide synthase family enzymatic basis for the preference of FA chain length
J. Lipid Res.
49
2356-2364
2008
Homo sapiens (P27544)
brenda
Couttas, T.A.; Lim, X.Y.; Don, A.S.
A three-step assay for ceramide synthase activity using a fluorescent substrate and HPLC
Lipids
50
101-109
2015
Homo sapiens (P27545)
brenda
Lim, X.Y.; Pickford, R.; Don, A.S.
Assaying ceramide synthase activity in vitro and in living cells using liquid chromatography-mass spectrometry
Methods Mol. Biol.
1376
11-22
2016
Homo sapiens (P27544)
brenda
Separovic, D.; Breen, P.; Joseph, N.; Bielawski, J.; Pierce, J.S.; VAN Buren, E.; Gudz, T.I.
siRNA-mediated down-regulation of ceramide synthase 1 leads to apoptotic resistance in human head and neck squamous carcinoma cells after photodynamic therapy
Anticancer Res.
32
2479-2485
2012
Homo sapiens
brenda
Mullen, T.D.; Hannun, Y.A.; Obeid, L.M.
Ceramide synthases at the centre of sphingolipid metabolism and biology
Biochem. J.
441
789-802
2012
Homo sapiens, Mus musculus
brenda
Turpin-Nolan, S.M.; Hammerschmidt, P.; Chen, W.; Jais, A.; Timper, K.; Awazawa, M.; Brodesser, S.; Bruening, J.C.
CerS1-derived C18 0 ceramide in skeletal muscle promotes obesity-induced insulin resistance
Cell Rep.
26
1-10.e7
2019
Mus musculus
brenda
Venkataraman, K.; Riebeling, C.; Bodennec, J.; Riezman, H.; Allegood, J.C.; Sullards, M.C.; Merrill, A.H.Jr.; Futerman, A.H.
Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells
J. Biol. Chem.
277
35642-35649
2002
Mus musculus (P27545)
brenda
Kim, H.J.; Qiao, Q.; Toop, H.D.; Morris, J.C.; Don, A.S.
A fluorescent assay for ceramide synthase activity
J. Lipid Res.
53
1701-1707
2012
Homo sapiens
brenda
Couttas, T.; Don, A.
Fluorescent assays for ceramide synthase activity
Methods Mol. Biol.
1376
23-33
2016
Homo sapiens
brenda
Wang, Z.; Wen, L.; Zhu, F.; Wang, Y.; Xie, Q.; Chen, Z.; Li, Y.
Overexpression of ceramide synthase 1 increases C18-ceramide and leads to lethal autophagy in human glioma
Oncotarget
8
104022-104036
2017
Homo sapiens
brenda