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Gene Review

Cyp4g1  -  Cytochrome P450-4g1

Drosophila melanogaster

Synonyms: 4g1, ASC-T1, CG3972, CYPIVG1, Cyt-P450-A1, ...
 
 
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Disease relevance of Cyp4g1

 

High impact information on Cyp4g1

  • Using the Somatic Mutation And Recombination Test (SMART) we have demonstrated that transgenic larvae expressing the P450 are hypersensitive to the anticancer drug cyclophosphamide, a procarcinogenic substrate which is activated by the enzyme [2].
  • In this study we have used precise genetic mapping to identify a mechanism of lufenuron resistance: the overexpression of the cytochrome P450 gene Cyp12a4 [3].
  • The 5' flanking sequence of one gene in this region, Cyp6g1 (a cytochrome P450), is nearly fixed for a Doc transposable element insertion [4].
  • Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone [5].
  • The present data show that the wild-type genes of two members of the Halloween family of embryonic lethals, disembodied (dib) and shadow (sad), code for mitochondrial cytochromes P450 that mediate the last two hydroxylation reactions in the ecdysteroidogenic pathway in Drosophila, namely the C22- and C2-hydroxylases [6].
 

Biological context of Cyp4g1

 

Anatomical context of Cyp4g1

  • This is the first indication of a specific P450 expressed in the central nervous system of Drosophila, and the putative function of the corresponding enzyme is discussed [9].
  • Furthermore, analysis of c/ebp beta-deficient mice shows that mutant animals are defective in expression of a murine CYP2D5 homolog in hepatic cells, confirming the selective ability of C/EBP beta to activate this liver-specific P-450 gene in vivo [10].
  • In contrast, increases in the rate of BP turnover per molecule of cytochrome P-450, intensity of the hemoprotein band with apparent molecular weight 56,000 and the yield of BP 7,8-dihydrodiol and 9,10-dihydrodiol occurred only in microsomes of BP-pretreated 364yv flies but not of Turku ones [11].
  • Feeding of these compounds in combination with the inhibition of cytochrome P-450 by 1-phenylimidazole (PhI) allowed sufficient quantities of the mutagen to reach the gonads and to produce significant genetic damage [12].
  • These results indicate that the fat body participates in the P450-mediated metabolism of excess furanocoumarins unmetabolized by the midgut [13].
 

Associations of Cyp4g1 with chemical compounds

  • Cytochrome P450 monooxygenases, a family of detoxifying enzymes, are thought to confer resistance to various insecticides including DDT [14].
  • The effect of xenobiotics (phenobarbital and atrazine) on the expression of Drosophila melanogaster CYP genes encoding cytochromes P450, a gene family generally associated with detoxification, was analyzed by DNA microarray hybridization and verified by real-time RT-PCR in adults of both sexes [15].
  • In addition, they specifically express many different lipid-metabolizing proteins, including Cyp4g1, an omega-hydroxylase regulating triacylglycerol composition [16].
  • Significant purification of the ubiquitous cytochrome P-450-A and the strain-specific P-450-B from Drosophila melanogaster has been achieved by sequential chromatography on octylamino-agarose, DEAE-cellulose and hydroxyapatite [17].
  • Five different enzymatic activities, catalyzed by both microsomal and mitochondrial cytochrome P450 monooxygenases (CYPs), are strongly implicated in the biosynthesis of ecdysone (E) from cholesterol [6].
 

Other interactions of Cyp4g1

  • The insert is located at the 3' end of the cyp12a4 gene that belongs to the cytochrome P450 family [18].
 

Analytical, diagnostic and therapeutic context of Cyp4g1

  • Preparations of P-450-A (specific contents of 7-9 nmol/mg) were homogeneous as determined by SDS/polyacrylamide-gel electrophoresis (PAGE) analysis [17].
  • Sequence alignments were used to draw phylogenetic trees and to analyze the intron-exon organization of each functional P450 gene [8].
  • A novel cytochrome P450 was isolated from Drosophila melanogaster by PCR strategy with primers deduced from the crayfish Orconectes limosus CYP4C15 sequence, which is supposed to be involved in ecdysteroid biosynthesis [9].
  • Using cDNA array techniques, the transcriptional levels of Drosophila cytochrome P450 (P450) genes were compared between male and female flies [19].
  • P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature [20].

References

  1. Relation between the somatic toxicity of dimethylnitrosamine and a genetically determined variation in the level and induction of cytochrome P450 in Drosophila melanogaster. Hällström, I., Magnusson, J., Ramel, C. Mutat. Res. (1982) [Pubmed]
  2. Mammalian genes expressed in Drosophila: a transgenic model for the study of mechanisms of chemical mutagenesis and metabolism. Jowett, T., Wajidi, M.F., Oxtoby, E., Wolf, C.R. EMBO J. (1991) [Pubmed]
  3. Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster. Bogwitz, M.R., Chung, H., Magoc, L., Rigby, S., Wong, W., O'Keefe, M., McKenzie, J.A., Batterham, P., Daborn, P.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Strong selective sweep associated with a transposon insertion in Drosophila simulans. Schlenke, T.A., Begun, D.J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone. Petryk, A., Warren, J.T., Marqués, G., Jarcho, M.P., Gilbert, L.I., Kahler, J., Parvy, J.P., Li, Y., Dauphin-Villemant, C., O'Connor, M.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Molecular and biochemical characterization of two P450 enzymes in the ecdysteroidogenic pathway of Drosophila melanogaster. Warren, J.T., Petryk, A., Marques, G., Jarcho, M., Parvy, J.P., Dauphin-Villemant, C., O'Connor, M.B., Gilbert, L.I. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Cis-Regulatory Elements in the Accord Retrotransposon Result in Tissue-Specific Expression of the Drosophila melanogaster Insecticide Resistance Gene Cyp6g1. Chung, H., Bogwitz, M.R., McCart, C., Andrianopoulos, A., Ffrench-Constant, R.H., Batterham, P., Daborn, P.J. Genetics (2007) [Pubmed]
  8. The cytochrome P450 gene superfamily in Drosophila melanogaster: annotation, intron-exon organization and phylogeny. Tijet, N., Helvig, C., Feyereisen, R. Gene (2001) [Pubmed]
  9. A new cytochrome P450 from Drosophila melanogaster, CYP4G15, expressed in the nervous system. Maïbèche-Coisne, M., Monti-Dedieu, L., Aragon, S., Dauphin-Villemant, C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  10. The ability of C/EBP beta but not C/EBP alpha to synergize with an Sp1 protein is specified by the leucine zipper and activation domain. Lee, Y.H., Williams, S.C., Baer, M., Sterneck, E., Gonzalez, F.J., Johnson, P.F. Mol. Cell. Biol. (1997) [Pubmed]
  11. Xenobiotic-metabolizing enzymes and benzo[a]pyrene metabolism in the benzo[a]pyrene-sensitive mutant strain of Drosophila simulans. Fuchs SYu, n.u.l.l., Spiegelman, V.S., Safaev, R.D., Belitsky, G.A. Mutat. Res. (1992) [Pubmed]
  12. Metabolic inactivation of mutagens in Drosophila melanogaster. Zijlstra, J.A., Vogel, E.W. Mutat. Res. (1988) [Pubmed]
  13. Expression of CYP6B1 and CYP6B3 cytochrome P450 monooxygenases and furanocoumarin metabolism in different tissues of Papilio polyxenes (Lepidoptera: Papilionidae). Petersen, R.A., Zangerl, A.R., Berenbaum, M.R., Schuler, M.A. Insect Biochem. Mol. Biol. (2001) [Pubmed]
  14. High expression of Cyp6g1, a cytochrome P450 gene, does not necessarily confer DDT resistance in Drosophila melanogaster. Kuruganti, S., Lam, V., Zhou, X., Bennett, G., Pittendrigh, B.R., Ganguly, R. Gene (2007) [Pubmed]
  15. Xenobiotic response in Drosophila melanogaster: sex dependence of P450 and GST gene induction. Le Goff, G., Hilliou, F., Siegfried, B.D., Boundy, S., Wajnberg, E., Sofer, L., Audant, P., ffrench-Constant, R.H., Feyereisen, R. Insect Biochem. Mol. Biol. (2006) [Pubmed]
  16. Specialized hepatocyte-like cells regulate Drosophila lipid metabolism. Gutierrez, E., Wiggins, D., Fielding, B., Gould, A.P. Nature (2007) [Pubmed]
  17. Isolation of insecticide resistance-related forms of cytochrome P-450 from Drosophila melanogaster. Sundseth, S.S., Nix, C.E., Waters, L.C. Biochem. J. (1990) [Pubmed]
  18. Evidence for a functional interaction between the Bari1 transposable element and the cytochrome P450 cyp12a4 gene in Drosophila melanogaster. Marsano, R.M., Caizzi, R., Moschetti, R., Junakovic, N. Gene (2005) [Pubmed]
  19. Male specific expression of a cytochrome P450 (Cyp312a1) in Drosophila melanogaster. Kasai, S., Tomita, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  20. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Nelson, D.R., Koymans, L., Kamataki, T., Stegeman, J.J., Feyereisen, R., Waxman, D.J., Waterman, M.R., Gotoh, O., Coon, M.J., Estabrook, R.W., Gunsalus, I.C., Nebert, D.W. Pharmacogenetics (1996) [Pubmed]
 
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