CYP26A1 explained

Cytochrome P450 26A1 is a protein that in humans is encoded by the CYP26A1 gene.^{[1] [2] [3]}

Function

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This endoplasmic reticulum protein acts on retinoids, including all-trans-retinoic acid (RA), with both 4-hydroxylation and 18-hydroxylation activities. This enzyme regulates the cellular level of retinoic acid which is involved in regulation of gene expression in both embryonic and adult tissues. Two alternatively spliced transcript variants of this gene, which encode the distinct isoforms, have been reported.

CYP26A1 is over-expressed in colorectal cancer cells compared to normal colonic epithelium but is of no independent prognostic value in patients with colorectal cancer.^[4]

References

Further reading

• Duell EA, Kang S, Voorhees JJ . Retinoic acid isomers applied to human skin in vivo each induce a 4-hydroxylase that inactivates only trans retinoic acid . The Journal of Investigative Dermatology . 106 . 2 . 316–20 . February 1996 . 8601734 . 10.1111/1523-1747.ep12342972 . free .
• Ray WJ, Bain G, Yao M, Gottlieb DI . CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family . The Journal of Biological Chemistry . 272 . 30 . 18702–8 . July 1997 . 9228041 . 10.1074/jbc.272.30.18702 . free .
• Sonneveld E, van den Brink CE, van der Leede BM, Schulkes RK, Petkovich M, van der Burg B, van der Saag PT . Human retinoic acid (RA) 4-hydroxylase (CYP26) is highly specific for all-trans-RA and can be induced through RA receptors in human breast and colon carcinoma cells . Cell Growth & Differentiation . 9 . 8 . 629–37 . August 1998 . 9716180 .
• Trofimova-Griffin ME, Juchau MR . Expression of cytochrome P450RAI (CYP26) in human fetal hepatic and cephalic tissues . Biochemical and Biophysical Research Communications . 252 . 2 . 487–91 . November 1998 . 9826557 . 10.1006/bbrc.1998.9659 .
• Popa C, Dicker AJ, Dahler AL, Saunders NA . Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid-inducible . The British Journal of Dermatology . 141 . 3 . 460–8 . September 1999 . 10583049 . 10.1046/j.1365-2133.1999.03039.x . 19697736 .
• McSorley LC, Daly AK . Identification of human cytochrome P450 isoforms that contribute to all-trans-retinoic acid 4-hydroxylation . Biochemical Pharmacology . 60 . 4 . 517–26 . August 2000 . 10874126 . 10.1016/S0006-2952(00)00356-7 .
• Loudig O, Babichuk C, White J, Abu-Abed S, Mueller C, Petkovich M . Cytochrome P450RAI(CYP26) promoter: a distinct composite retinoic acid response element underlies the complex regulation of retinoic acid metabolism . Molecular Endocrinology . 14 . 9 . 1483–97 . September 2000 . 10976925 . 10.1210/mend.14.9.0518 . free .
• Deng L, Shipley GL, Loose-Mitchell DS, Stancel GM, Broaddus R, Pickar JH, Davies PJ . Coordinate regulation of the production and signaling of retinoic acid by estrogen in the human endometrium . The Journal of Clinical Endocrinology and Metabolism . 88 . 5 . 2157–63 . May 2003 . 12727970 . 10.1210/jc.2002-021844 . free .
• Won JY, Nam EC, Yoo SJ, Kwon HJ, Um SJ, Han HS, Kim SH, Byun Y, Kim SY . The effect of cellular retinoic acid binding protein-I expression on the CYP26-mediated catabolism of all-trans retinoic acid and cell proliferation in head and neck squamous cell carcinoma . Metabolism . 53 . 8 . 1007–12 . August 2004 . 15281009 . 10.1016/j.metabol.2003.12.015 .
• Loudig O, Maclean GA, Dore NL, Luu L, Petkovich M . Transcriptional co-operativity between distant retinoic acid response elements in regulation of Cyp26A1 inducibility . The Biochemical Journal . 392 . Pt 1 . 241–8 . November 2005 . 16053444 . 1317683 . 10.1042/BJ20050874 .
• Ozpolat B, Mehta K, Lopez-Berestein G . Regulation of a highly specific retinoic acid-4-hydroxylase (CYP26A1) enzyme and all-trans-retinoic acid metabolism in human intestinal, liver, endothelial, and acute promyelocytic leukemia cells . Leukemia & Lymphoma . 46 . 10 . 1497–506 . October 2005 . 16194896 . 10.1080/10428190500174737 . 12269201 .
• Heise R, Mey J, Neis MM, Marquardt Y, Joussen S, Ott H, Wiederholt T, Kurschat P, Megahed M, Bickers DR, Merk HF, Baron JM . Mosaad Megahed . Skin retinoid concentrations are modulated by CYP26AI expression restricted to basal keratinocytes in normal human skin and differentiated 3D skin models . The Journal of Investigative Dermatology . 126 . 11 . 2473–80 . November 2006 . 16778795 . 10.1038/sj.jid.5700432 . free .
• Rat E, Billaut-Laden I, Allorge D, Lo-Guidice JM, Tellier M, Cauffiez C, Jonckheere N, van Seuningen I, Lhermitte M, Romano A, Guéant JL, Broly F . Evidence for a functional genetic polymorphism of the human retinoic acid-metabolizing enzyme CYP26A1, an enzyme that may be involved in spina bifida . Birth Defects Research. Part A, Clinical and Molecular Teratology . 76 . 6 . 491–8 . June 2006 . 16933217 . 10.1002/bdra.20275 .
• Gomaa MS, Yee SW, Milbourne CE, Barbera MC, Simons C, Brancale A . Homology model of human retinoic acid metabolising enzyme cytochrome P450 26A1 (CYP26A1): active site architecture and ligand binding . Journal of Enzyme Inhibition and Medicinal Chemistry . 21 . 4 . 361–9 . August 2006 . 17059167 . 10.1080/14756360600742014 . 20519075 .
• Quere R, Baudet A, Cassinat B, Bertrand G, Marti J, Manchon L, Piquemal D, Chomienne C, Commes T . Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity . Blood . 109 . 10 . 4450–60 . May 2007 . 17218384 . 10.1182/blood-2006-10-051086 . 1494837 . free .
• Lee SJ, Perera L, Coulter SJ, Mohrenweiser HW, Jetten A, Goldstein JA . The discovery of new coding alleles of human CYP26A1 that are potentially defective in the metabolism of all-trans retinoic acid and their assessment in a recombinant cDNA expression system . Pharmacogenetics and Genomics . 17 . 3 . 169–80 . March 2007 . 17460545 . 2393551 . 10.1097/FPC.0b013e32801152d6 .

Notes and References

1. White JA, Beckett-Jones B, Guo YD, Dilworth FJ, Bonasoro J, Jones G, Petkovich M . cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450 . The Journal of Biological Chemistry . 272 . 30 . 18538–41 . July 1997 . 9228017 . 10.1074/jbc.272.30.18538 . free .
2. White JA, Beckett B, Scherer SW, Herbrick JA, Petkovich M . P450RAI (CYP26A1) maps to human chromosome 10q23-q24 and mouse chromosome 19C2-3 . Genomics . 48 . 2 . 270–2 . March 1998 . 9521883 . 10.1006/geno.1997.5157 .
3. Web site: Entrez Gene: CYP26A1 cytochrome P450, family 26, subfamily A, polypeptide 1.
4. Brown GT, Cash BG, Blihoghe D, Johansson P, Alnabulsi A, Murray GI . The expression and prognostic significance of retinoic acid metabolising enzymes in colorectal cancer . PLOS ONE . 9 . 3 . e90776 . 2014-03-07 . 24608339 . 10.1371/journal.pone.0090776 . 3946526. 2014PLoSO...990776B . free .