c-Myc represses the murine Nramp1 promoter.
The Nramp1 (natural resistance-associated macrophage protein 1) gene modulates the growth of intracellular pathogens and encodes a divalent cation transporter within lysosomes/late endosomes of macrophages. Nramp1 modulates the cytoplasmic iron pool. Wu, Polack and Dalla-Favera [(1999) Science 283, 676-679] showed reciprocal control of H-ferritin and IRP2 by c-Myc, and suggest that c-Myc regulates genes to increase cytoplasmic iron. A role for c-Myc in Nramp1 regulation was evaluated. Co-transfection studies show that c-Myc represses Nramp1 promoter function. Five non-canonical Myc-max binding sites (E-box) identified within the Nramp1 5'-flanking sequence are not responsible for the inhibitory effects of c-Myc on Nramp1 expression. An initiator(s) adjacent to the transcription-initiation site is a candidate for the inhibition observed. Results are consistent with a role for Nramp1 removing iron from the cytosol and antagonizing c-Myc function.
Bowen
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H
Biochemistry and Molecular Biology, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Biggs
T E
TE
Baker
S T
ST
Phillips
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E
Perry
V H
VH
Mann
D A
DA
Barton
C H
CH
D000818:Animals; D001665:Binding Sites; D027682:Cation Transport Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D016259:Genes, myc; D051379:Mice; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D015183:Restriction Mapping; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D011994:Recombinant Proteins; D014157:Transcription Factors; D000099173:Natural Resistance-associated Macrophage Protein 1