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malfunction
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DHCR24 knockout mice die within a few hours after birth. Cultured metatarsal bones from newborn knockout mice show a significant retarded growth. Absence of proliferating chondrocytes in the growth plate and abnormal hypertrophy of prehypertrophic chondrocytes are observed in the bones from knockout mice
malfunction
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DHCR24 overexpressed in CHO cells show that untreated CHO-DHCR24 cells have a higher cholesterol to desmosterol ratio. In the CHO-DHCR24 cells, more 24(S),25-epoxycholesterol is required to attain the same cholesterol to desmosterol ratio as in CHO cells expressing an empty vector. Thus, with DHCR24 overexpression, the effect of 24(S),25-epoxycholesterol on the cholesterol to desmosterol ratio is blunted
malfunction
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insulin-induced reactive oxygen species production is enhanced by siRNA for DHCR24
malfunction
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overexpression of DHCR24 protects ATDC5 cells from H2O2-induces hypertrophy. Insulin-induced hypertrophic differentiation of ATDC5 cells is associated with production of reactive oxygen species and pretreatment of the cells with siRNA for DHCR24 mRNA accelerates the hypertrophic differentiation
malfunction
(A-I)rHDL-mediated induction of HO-1 is reduced in human coronary artery endothelial cells transfected with DHCR24 siRNA. The activation of phosphatidylinositol 3-kinase/Akt by (A-I)rHDL is decreased in human coronary artery endothelial cells that are transfected with DHCR24 siRNA
malfunction
2-152a MAb-mediated binding of a cytotoxic agent (a saponin-conjugated secondary antibody) to surface DHCR24 leads to significant cytotoxicity. HCV replication can be suppressed by inhibiting DHCR24 with an enzymatic inhibitor
malfunction
loss of DHCR24 results in severe developmental and growth defects. Missense mutations in DHCR24, which result in diminished protein activity, can lead to a rare autosomal recessive disorder, desmosterolosis. The single nucleotide polymorphism, rs600491 (T allele) is significantly correlating with Alzheimer's disease risk in men. Four single nucleotide polymorphisms in the DHCR24 promoter correlate with hepatitis C virus (HCV) induced hepatocellular carcinoma and cirrhosis. The enzyme can be involved in Alzheimer's disease and is downregulated in affected regions of Alzheimer's disease (AD) brains, Overexpressing DHCR24 in cell culture protects cells from apoptosis, through inhibiting caspase-3 and amyloid beta toxicity. DHCR24 is implicated in the anti-inflammatory effects of HDL and resulting cardiovascular disease. Altered expression of a subset of androgen receptor-related genes, such as DHCR24, is observed in prostate cancer, overexpression of DHCR24 is a hallmark of prostate cancer, with high levels observed in low-grade prostate cancer, which diminish as the cancer progresses to a higher grade
malfunction
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loss of DWF1 results in severe developmental and growth defects
malfunction
mutating residues T110, Y299, and Y507 of known phosphorylation sites inhibits DHCR24 activity. Seven missense mutations in DHCR24 have been described in desmosterolosis: R94H, R103C, E191K, N294T, K306N, Y471S, E480K. PKC inhibition results in desmosterol accumulation
malfunction
overexpression of DHCR24 enhances 7-dehydrocholesterol reductase, DHCR7, activity, but only when a functional form of DHCR24 is used. When the DHCR24 gene is knocked down by siRNA, DHCR7 activity is also ablated. Knockdown of DHCR7 has no effect on DHCR24 activity, while knockdown of DHCR24 decreases DHCR7 activity by about 60%
malfunction
the enzyme dim mutant plants, similarly to the dwarf5-2, show a dwarf phenotype due to the deficiency in brassinosteroids, caused by a block in the D24-sterol-D24-reductase activity. Compared to the wild-type, the dim plants show reduced levels of campesterol and sitosterol associated to an increase of 24-methylene cholesterol and isofucosterol, their respective metabolic precursors and substrates of DIM. Mutant dim seedlings have short hypocotyls, petioles, and roots. Leaves of dim are round, curly, and dark green in color. In adult flowering plants, dim shows extremely short inflorescences with small flowers and severely reduced fertility. Phenotype, overview
malfunction
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enzyme inhibition leads to increased inflammation resolution and selectively decreases proinflammatory cell influx
malfunction
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the blockade of the enzyme activity impairs adhesion, migration and proliferation of vascular smooth muscle cells
malfunction
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the enzyme dim mutant plants, similarly to the dwarf5-2, show a dwarf phenotype due to the deficiency in brassinosteroids, caused by a block in the D24-sterol-D24-reductase activity. Compared to the wild-type, the dim plants show reduced levels of campesterol and sitosterol associated to an increase of 24-methylene cholesterol and isofucosterol, their respective metabolic precursors and substrates of DIM. Mutant dim seedlings have short hypocotyls, petioles, and roots. Leaves of dim are round, curly, and dark green in color. In adult flowering plants, dim shows extremely short inflorescences with small flowers and severely reduced fertility. Phenotype, overview
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metabolism
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desmosterol suffice as a cholesterol replacement. Although a wide range of sterols and cholesterol analogues such as beta-sitosterol, ergosterol and 5beta-cholestan-3beta-ol are unable to support cell proliferation, 5alpha-cholestan-3beta-ol, i.e. dihydrocholesterol, and desmosterol can
metabolism
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desmosterol suffice as a cholesterol replacement. Although a wide range of sterols and cholesterol analogues such as beta-sitosterol, ergosterol and 5beta-cholestan-3beta-ol are unable to support cell proliferation, while 5alpha-cholestan-3beta-ol, i.e. dihydrocholesterol, can do so, pathway regulation, detailed overview
metabolism
DHCR24 catalyzes the ultimate step in the Bloch pathway of cholesterol synthesis
metabolism
DHCR24 is the final enzyme in cholesterol synthesis, role of signaling in regulating cholesterol homeostasis
metabolism
substrate channeling in the cholesterol metabolon of choleterol biosynthesis, cholesterol synthesis proteins identified by LC-MS/MS after DHCR24 immunoprecipitation
metabolism
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the enzyme catalyzes the final step in cholesterol biosynthesis
metabolism
the enzyme is involved in the sterol biosynthetic pathway in Arabidopsis thaliana, overview
metabolism
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biosynthesis of 24-methylene brassinosteroid is an alternative route for generating castasterone, which is mediated and regulated by the enzyme in Arabidopsis thaliana
metabolism
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isoform DHCR24-1 but not DHCR24-2 contributes to conversion of phytosterols to cholesterol mainly in the midgut of Bombyx mori larvae
metabolism
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the enzyme is involved in the sterol biosynthetic pathway in Arabidopsis thaliana, overview
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physiological function
3beta-hydroxysteroid-DELTA24 reductase (DHCR24) is an endoplasmic reticulum-localized multifunctional enzyme that possesses anti-apoptotic and cholesterol-synthesizing activities. Overexpression of DHCR24 protects neuronal cells from tunicamycin-induced apoptosis. DHCR24 may function as a neuroprotective protein under endoplasmic reticulum stress. Overexpression of DHCR24 inhibits apoptotic cell signaling and reduces or delays activation of endoplasnic reticlum stress-related cell signaling during unfolded protein response in mouse embryonic fibroblast N2A cells, overview. Elevated cholesterol levels may contribute to the neuroprotective function of DHCR24
physiological function
ArDWF1 functions as the sole enzyme responsible for biosynthesis of 24-methylcholesterol in the Ajuga plant
physiological function
as well as playing an essential role in the regulation of cholesterol synthesis, DHCR24 is important in other cellular processes, such as signaling, the formation of lipid rafts, mediating cell stress responses, and regulating steroidogenesis, in steroidogenesis and bile acid synthesis, cell survival, and chlolesterol homeostasis and membranes. DHCR24 is modulating oxidative stress. DHCR24 or seladin-1 plays an important role in stress signaling and apoptosis: up-regulated in response to cell stress (oxidative- and amyloid b-toxicity) promoting cell survival by inhibiting caspase-3 activation, and deactivated by caspase cleavage during apoptosis. The enzyme is regulated by the following transcription factors/proteins: sterol regulatory element binding protein 2, nuclear factor Y (via methylation), specificity protein 1, estrogen receptor, androgen receptor, thyroid hormone receptor, constitutive androstane receptor, and pregnane X receptor
physiological function
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invertebrates such as Bombyx mori (silkworm), which cannot perform de novo cholesterol synthesis, also possess a DHCR24 homologue. This protein provides the organism with cholesterol by transformation of dietary phytosterols through a dealkylation reaction, similar to the DWF1 catalyzed reaction from Arabidopsis thaliana. Furthermore, this reaction is FAD and NADPH dependent
physiological function
lipid-free apoA-I and (A-I)rHDL inhibit inflammation by increasing DHCR24 expression, which, in turn, activates phosphatidylinositol 3-kinase/Akt and induces HO-1
physiological function
surface DHCR24 on hepatocellular carcinoma cells can function as a carrier for internalization, e.g. of hepatitis C virus, HCV. DHCR24-mediated cholesterol biosynthesis plays a crucial role in the HCV life cycle. Antibody 2-152a MAb-mediated binding of 2ndAb-Sap to surface DHCR24 on hepatocellular carcinoma cells predicted to lead to internalization of 2ndAb-Sap and subsequent cell death
physiological function
the enzyme activity is regulated by signaling through kinases and reversible phosphorylation
physiological function
the enzyme DELTA24-sterol reductase DHCR24 is involved in the cholesterol biosynthesis catalyzing the reduction of desmosterol to cholesterol. DHCR24 controls the activity of 7-dehydrocholesterol , DHCR7, which is important for both cholesterol and vitamin D synthesis. DHCR24 is involved in a remarkable diversity of cellular functions (e.g., oxidative stress, neuroprotection, cell survival), and is implicated in many diseases including cardiovascular disease, hepatitis C, certain cancers, and neurodegenerative diseases
physiological function
the enzyme has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid beta deposition
physiological function
the enzyme has neuroprotective and cholesterol-synthesizing activities. DHCR24 overexpression confers neuroprotection against apoptosis caused by amyloid beta deposition
physiological function
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the enzyme is an important protein in plant sterol (phytosterol) and steroid (brassinosteroid) synthesis, by catalyzing the isomerisation of the DELTA24(28) bond, and the subsequent reduction of the DELTA24(25) bond in various sterol precursors
physiological function
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the enzyme functions in biosynthesis of active brassinosteroids in Arabidopsis thaliana. Enzyme overexpression enhances growth and development in Arabidopsis
additional information
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J774 cells, that lack a full-length transcript for DHCR24, consequently accumulate desmosterol
additional information
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J774 cells, that lack a full-length transcript for DHCR24, consequently accumulate desmosterol
additional information
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the hepatitis C virus-expressing hepatoblastoma-derived cell line, RzM6-LC, shows augmented tumorigenicity. DHCR24 expression reflects tumorigenicity, overview. Ectopic or HCV-induced DHCR24 overexpression results in resistance to oxidative stress-induced apoptosis and suppressed p53 activity. DHCR24 overexpression in these cells paralleles the increased interaction between p53 and MDM2, a p53-specific E3 ubiquitin ligase, in the cytoplasm. Persistent DHCR24 overexpression does not alter the phosphorylation status of p53 but results in decreased acetylation of p53 at Lys residues 373 and 382 in the nucleus after treatment with H2O2. DHCR24 overexpression inhibits polyubiquitination in RzM6-LC cells and H358, p53 null, cells. Ectopic expression of DHCR24 does not inhibit apoptotic response to H2O2 in WI38 cells
additional information
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while cholesterol itself may not be unique in its ability to sustain mammalian life, sterols very much like cholesterol, such as desmosterol, appear to be absolutely required
additional information
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while cholesterol itself may not be unique in its ability to sustain mammalian life, sterols very much like cholesterol, such as desmosterol, appear to be absolutely required
additional information
ArDWF1 has another unique property in that only campesterol is formed by the direct reduction catalyzed by the enzyme. Ajuga plants have unique sterol profiles in which clerosterol and dehydroclerosterol are the major sterols