Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid metabolism in F9 cells are regulated by retinoic acid receptor gamma and retinoid X receptor alpha.
Fiche publication
Date publication
janvier 1998
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr METZGER Daniel
Tous les auteurs :
Abu-Abed SS, Beckett BR, Chiba H, Chithalen JV, Jones G, Metzger D, Chambon P, Petkovich M
Lien Pubmed
Résumé
We have cloned a mouse cDNA homolog of P450RAI, a cytochrome P450 belonging to a new family (CYP26), which has previously been isolated from zebrafish and human cDNAs and found to encode a retinoic acid-inducible retinoic acid hydroxylase activity. The cross-species conservation of the amino acid sequence is high, particularly between the mouse and the human enzymes, in which it is over 90%. Like its human and zibrafish counterparts, the mouse P450RAI cDNA catalyzes metabolism of retinoic acid into 4-OH-retinoic acid, 4-oxo-retinoic acid, 18-OH-retinoic acid, and unidentified water-soluble metabolites when transfected into COS-1 cells. Retinoic acid-inducible retinoic acid metabolism has previously been observed in F9 murine embryonal carcinoma cells and some derivatives lacking retinoid receptors. We were interested in determining whether P450RAI could be responsible for retinoic acid metabolism in F9 cells and in studying the effect of retinoid receptor ablation on P450RAI expression. In wild-type F9 cells and derivatives lacking RAR gamma, RAR alpha, and/or RXR alpha, we observed a direct relationship between the level of retinoic acid metabolic activity and retinoic acid-induced P450RAI mRNA. These experiments, as well as others using synthetic receptor subtype-specific retinoids, suggest that the RAR gamma and RXR alpha receptors mediate the effects of retinoic acid on the expression of the P450RAI gene.
Mots clés
Amino Acid Sequence, Animals, Cloning, Molecular, Cytochrome P-450 Enzyme System, biosynthesis, Enzyme Induction, Humans, Mice, Mixed Function Oxygenases, biosynthesis, Molecular Sequence Data, Polymerase Chain Reaction, Receptors, Retinoic Acid, metabolism, Retinoic Acid 4-Hydroxylase, Retinoid X Receptors, Sequence Alignment, Transcription Factors, metabolism, Tretinoin, metabolism, Tumor Cells, Cultured, Up-Regulation, Zebrafish
Référence
J. Biol. Chem.. 1998 Jan;273(4):2409-15