Characterization of DNA-binding proteins required for glucocorticoid induction of CYP3A23

Archives of Biochemistry and Biophysics
Linda C QuattrochiPhilip S Guzelian

Abstract

Cytochrome P450 (CYP) 3A23 is transcriptionally regulated in rat liver by such glucocorticoids as dexamethasone (DEX) and by such antiglucocorticoids as pregnenolone 16 alpha-carbonitrile (PCN). Based on studies of CYP3A23 gene fragments expressed in primary cultures of adult rat hepatocytes and tested for DNA-protein interactions, we have proposed that the mechanism of CYP3A23 induction by these steroid hormones involves the glucocorticoid receptor or a protein induced by glucocorticoids indirectly interacting with proteins constitutively bound to an enhancer element consisting of a direct repeat of 7-bp separated by two nucleotides in the 5'-flanking region of the CYP3A23 gene (L. Quattrochi et al., J. Biol. Chem. 270, 28,917, 1995). In the present study, we prepared and transiently expressed in cultured rat hepatocytes 20-bp double-stranded (ds)-oligonucleotides containing this direct repeat or various mutations of this direct repeat inserted into a chloramphenicol acetyltransferase (CAT) reporter plasmid. We found that both repeats were necessary for induction of CAT by either DEX or PCN. Analysis of proteins bound to CYP3A23 enhancer through the use of uv cross-linking revealed two rat liver nuclear proteins with molecular...Continue Reading

References

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Citations

Jan 25, 2002·Annual Review of Pharmacology and Toxicology·Bryan GoodwinSteven A Kliewer
Oct 10, 2002·Endocrine Reviews·Steven A KliewerTimothy M Willson
Sep 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Judy RaucyScott W Allen
Mar 30, 2001·The Journal of Biological Chemistry·D SmirlisE A Shephard

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