title: Characterization of the adrenoleukodystrophy-related (ALDR, ABCD2) gene promoter: inductibility by retinoic acid and forskolin.
abstract: The adrenoleukodystrophy-related gene (ALDR, ABCD2) is a candidate modifier gene and a potential therapeutic target for X-linked adrenoleukodystrophy (ALD), a severe neurodegenerative disease. The ALDR gene is the closest homologue of the ALD gene, which encodes a peroxisomal ABC transporter involved in the catabolism of very-long-chain fatty acids. Administration of fenofibrate upregulates ALDR expression in rodent liver. As a step toward understanding ALDR transcriptional regulation, the mouse and human 5' regions were characterized. The human and mouse genes share a 500-bp conserved region that contains potential Sp1- and AP-2-binding sites but no TATA box. Analysis of the 5'-flanking region of ALDR using a luciferase reporter system revealed that 1.3 kb of human or mouse 5'-upstream region has functional promoter activity. In these transfection experiments, promoter activity of both human and mouse genes could be upregulated by 9-cis-retinoic acid and forskolin, while no effect of PPARalpha could be detected.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch Cedex, C.U. de Strasbourg, 67404, France.
authors.forename: A
authors.initials: A
authors.lastname: Pujol
authors.forename: N
authors.initials: N
authors.lastname: Troffer-Charlier
authors.forename: E
authors.initials: E
authors.lastname: Metzger
authors.forename: G
authors.initials: G
authors.lastname: Chimini
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
mesh_terms: D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000031:analogs & derivatives; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C431694:ABCD2 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D005576:Colforsin; D014212:Tretinoin; D000242:Cyclic AMP