title: Structure of the human steroidogenic acute regulatory protein (StAR) gene: StAR stimulates mitochondrial cholesterol 27-hydroxylase activity.
abstract: Steroidogenic acute regulatory protein (StAR) plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. We determined the organization of the StAR structural gene, mapped to 8p11.2. The gene spans 8 kb and consists of seven exons interrupted by six introns. The 1.3 kb of DNA upstream from the transcription start site directed expression of a luciferase reporter gene in mouse Y-1 adrenal cortical tumor cells but not in BeWo choriocarcinoma cells. Reporter gene expression in the Y-1 cells was increased more than 2-fold by 8-Br-cAMP, indicating that the 1.3 kb DNA fragment contains sequences that confer tissue-specific expression and cAMP regulation. The sequence of a related StAR pseudogene, mapped to chromosome 13, lacks introns and has an insertion, numerous substitutions, and deletions. Expression of StAR in COS-1 cells cotransfected with cholesterol 27-hydroxylase (P450c27) and adrenodoxin resulted in a 6-fold increase in formation of 3 beta-hydroxy-5-cholestenoic acid, demonstrating that StAR's actions are not specific to steroidogenesis but extend to other mitochondrial cholesterol-metabolizing enzymes.
authors.affiliation: Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia 19104, USA.
authors.forename: T
authors.initials: T
authors.lastname: Sugawara
authors.forename: D
authors.initials: D
authors.lastname: Lin
authors.forename: J A
authors.initials: JA
authors.lastname: Holt
authors.forename: K O
authors.initials: KO
authors.lastname: Martin
authors.forename: N B
authors.initials: NB
authors.lastname: Javitt
authors.forename: W L
authors.initials: WL
authors.lastname: Miller
authors.forename: J F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D000818:Animals; D001483:Base Sequence; D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004789:Enzyme Activation; D005796:Genes; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011544:Pseudogenes; D012689:Sequence Homology, Nucleic Acid; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C506832:Cyp27a1 protein, mouse