delta(24)-sterol reductase; 24-dehydrocholesterol reductase; 3-beta-hydroxysterol delta-24-reductase; diminuto/dwarf1 homolog; seladin-1 (DHCR24. KIAA0018)
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Function
- catalyzes reduction of delta-24 double bond of sterols
- final step in cholesterol biosynthesis
- converts desmosterol to cholesterol
- final step in cholesterol biosynthesis
- protects cells from oxidative stress
- inhibits apoptosis
- reduces caspase 3 activity during apoptosis induced by oxidative stress
- protects against amyloid-beta peptide-induced apoptosis
- upregulated in tumors[3][6]
- may be downstream regulator of estrogen receptor[5][8]
- during oncogenic & oxidative stress, Seladin-1
- binds p53 amino terminus
- displaces E3 ubiquitin ligase Mdm2 from p53
- results in p53 accumulation
- associates with Mdm2 independently of p53
- induces premature senescence in cells that would otherwise tranform[9]
Compartment
membrane-bound, endoplasmic reticulum Golgi
Expression
- expressed in brain (high levels)
- cortex, substantia nigra, caudate nucleus, hippocampus, medulla oblongata, pons
- expressed in adrenal gland (high levels)
- expressed in lesser amounts in:
- liver, lung, spleen, prostate spinal cord
- least expressed in: heart, uterus, prostate
- undetectable in blood cells, granulosa cell tumors[4]
Pathology
- in brains affected by Alzheimer's disease, expression in inferior temporal lobe < frontal cortex
- defects in DHCR24 are the cause of desmosterolosis [MIM:602398]. It is a
More general terms
Additional terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q15392.html
- ↑ Crameri A, Biondi E, Kuehnle K, Lutjohann D, Thelen KM, Perga S, Dotti CG, Nitsch RM, Ledesma MD, Mohajeri MH. The role of seladin-1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo. EMBO J. 2006 Jan 25;25(2):432-43. Epub 2006 Jan 12. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16407971
- ↑ 3.0 3.1 Luciani P, Gelmini S, Ferrante E, Lania A, Benvenuti S, Baglioni S, Mantovani G, Cellai I, Ammannati F, Spada A, Serio M, Peri A. Expression of the antiapoptotic gene seladin-1 and octreotide- induced apoptosis in growth hormone-secreting and nonfunctioning pituitary adenomas. J Clin Endocrinol Metab. 2005 Nov;90(11):6156-61. Epub 2005 Aug 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16091489
- ↑ 4.0 4.1 Fuller PJ, Alexiadis M, Jobling T, McNeilage J. Seladin-1/DHCR24 expression in normal ovary, ovarian epithelial and granulosa tumours. Clin Endocrinol (Oxf). 2005 Jul;63(1):111-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15963070
- ↑ 5.0 5.1 Peri A, Danza G, Serio M. Seladin-1 as a target of estrogen receptor activation in the brain: a new gene for a rather old story? J Endocrinol Invest. 2005 Mar;28(3):285-93. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15954227
- ↑ 6.0 6.1 Di Stasi D, Vallacchi V, Campi V, Ranzani T, Daniotti M, Chiodini E, Fiorentini S, Greeve I, Prinetti A, Rivoltini L, Pierotti MA, Rodolfo M. DHCR24 gene expression is upregulated in melanoma metastases and associated to resistance to oxidative stress-induced apoptosis. Int J Cancer. 2005 Jun 10;115(2):224-30. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15688385
- ↑ Ledesma MD, Dotti CG. The conflicting role of brain cholesterol in Alzheimer's disease: lessons from the brain plasminogen system. Biochem Soc Symp. 2005;(72):129-38. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15649137
- ↑ 8.0 8.1 Benvenuti S, Luciani P, Vannelli GB, Gelmini S, Franceschi E, Serio M, Peri A. Estrogen and selective estrogen receptor modulators exert neuroprotective effects and stimulate the expression of selective Alzheimer's disease indicator-1, a recently discovered antiapoptotic gene, in human neuroblast long-term cell cultures. J Clin Endocrinol Metab. 2005 Mar;90(3):1775-82. Epub 2004 Dec 7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15585566
- ↑ 9.0 9.1 Wu C, Miloslavskaya I, Demontis S, Maestro R, Galaktionov K. Regulation of cellular response to oncogenic and oxidative stress by Seladin-1. Nature. 2004 Dec 2;432(7017):640-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15577914
- ↑ Chen ZJ, Vulevic B, Ile KE, Soulika A, Davis W Jr, Reiner PB, Connop BP, Nathwani P, Trojanowski JQ, Tew KD. Association of ABCA2 expression with determinants of Alzheimer's disease. FASEB J. 2004 Jul;18(10):1129-31. Epub 2004 May 20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15155565
- ↑ Luciani P, Ferruzzi P, Arnaldi G, Crescioli C, Benvenuti S, Nesi G, Valeri A, Greeve I, Serio M, Mannelli M, Peri A. Expression of the novel adrenocorticotropin-responsive gene selective Alzheimer's disease indicator-1 in the normal adrenal cortex and in adrenocortical adenomas and carcinomas. J Clin Endocrinol Metab. 2004 Mar;89(3):1332-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15001630
- ↑ Iivonen S, Hiltunen M, Alafuzoff I, Mannermaa A, Kerokoski P, Puolivali J, Salminen A, Helisalmi S, Soininen H. Seladin-1 transcription is linked to neuronal degeneration in Alzheimer's disease. Neuroscience. 2002;113(2):301-10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12127087
- ↑ Greeve I, Hermans-Borgmeyer I, Brellinger C, Kasper D, Gomez-Isla T, Behl C, Levkau B, Nitsch RM. The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress. J Neurosci. 2000 Oct 1;20(19):7345-52. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11007892
- ↑ GeneReviews http://www.ncbi.nlm.nih.gov/sites/genetests/lab/gene/DHCR24