PMID: 9187262Jun 1, 1997Paper

DNA elements recognizing NF-Y and Sp1 regulate the human multidrug-resistance gene promoter

Molecular Pharmacology
R SundsethA C King

Abstract

Regulation of the human multidrug resistance gene (hMDR1) was studied by mapping DNA elements in the proximal promoter necessary for efficient transcription. Transient transfection analysis in tumor cell lines (HCT116, HepG2, and Saos2) of promoter deletions identified several regulatory domains. These cell lines expressed hMDR1 mRNA. Removal of an element between +25 and +158 reduced promoter activity by 2-3-fold, whereas deletion of sequences from approximately -5000 to -138 base pairs gave a approximately 2-fold increase. The activity of the hMDR1 promoter (-137 to +25) was comparable in activity to the SV40 early promoter and enhancer combination. Deletion of the hMDR1 promoter between -86 and -44 reduced activity by 5-10-fold, identifying an important regulatory region. This minimal region (-88 to -37) activated transcription when inserted upstream of a synthetic promoter, suggesting that it acts independently of other regulatory sequences. Two DNA elements within 85 base pairs of the transcriptional start site were required to confer efficient gene expression. A double-point mutation in the Y box (inverted CCAAT box) between -70 and -80 reduced activity of the promoter by 5-10-fold, and a single-point mutation at -52 with...Continue Reading

References

Jan 1, 1992·Acta Oncologica·A L Harris, D Hochhauser
Sep 16, 1992·Biochemical and Biophysical Research Communications·M MiyazakiM Kuwano
Dec 5, 1991·The New England Journal of Medicine·H S ChanV Ling
Jan 11, 1992·Nucleic Acids Research·S Faisst, S Meyer
Dec 25, 1991·Nucleic Acids Research·S L DanilitionN G Miyamoto
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·K E NoonanI B Roninson
Jan 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A T FojoI Pastan
Apr 7, 1989·Cell·S T Smale, D Baltimore
Dec 29, 1989·Biochemical and Biophysical Research Communications·K KohnoM Kuwano
Nov 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·C R FairchildK H Cowan
Apr 8, 1988·Cell·L A ChodoshP A Sharp
Sep 11, 1987·Cell·A DornD Mathis
Nov 1, 1995·Molecular and Cellular Biology·C McCoyM M Cornwell
Feb 24, 1995·The Journal of Biological Chemistry·G H MacDonaldJ P Ting
Mar 30, 1994·Biochemical and Biophysical Research Communications·K AsakunoM Kuwano

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Citations

Jan 23, 1999·The Journal of Biological Chemistry·J V ThottasseryJ D Schuetz
Mar 3, 2007·The Journal of Pharmacy and Pharmacology·Makrem Ben ReguigaRobert Farinotti
Feb 22, 2012·Biochemistry. Biokhimii︠a︡·I A EliseevaD N Lyabin
May 15, 2001·The Journal of Biological Chemistry·R A JohnsonK W Scotto
Jan 18, 2006·Drug Metabolism and Pharmacokinetics·Toshiyuki Sakaeda
Aug 26, 1998·The Journal of Biological Chemistry·J B Redell, B L Tempel
Nov 7, 2002·Biological & Pharmaceutical Bulletin·Toshiyuki SakaedaKatsuhiko Okumura
Oct 29, 2005·Chembiochem : a European Journal of Chemical Biology·Karen L BuchmuellerMoses Lee
Jan 25, 2000·The Journal of Biological Chemistry·Z HuK W Scotto
Jul 29, 2004·The Journal of Pharmacology and Experimental Therapeutics·Hiroshi TakaneIchiro Ieiri
Jul 30, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·David K Male
Mar 2, 2013·Cell Death and Differentiation·D Dolfini, R Mantovani
Mar 21, 2020·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Dahea YouLauren M Aleksunes
Dec 17, 2003·Pharmacology & Toxicology·Henrik GréenCurt Peterson
May 8, 1998·Biochemical and Biophysical Research Communications·H M Kauffmann, D Schrenk
Mar 7, 2001·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G J HooiveldM Müller
Dec 21, 2000·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·G J HooiveldM Müller
Aug 11, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Phillip KantharidisJohn Zalcberg
Sep 6, 2002·Biochemical Pharmacology·Stéphane LabialleLoris G Baggetto
Sep 10, 2003·Biochemical and Biophysical Research Communications·A GeierC Gartung
Oct 15, 2008·Biochemical Pharmacology·Ivanise Marina Moretti RebecchiRosario Dominguez Crespo Hirata

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