C-Myc represses the murine Nrampl promoter. (August 2002)

• Record Type: Journal Article
• Authors: Bowen, H.; Biggs, T. E.; Baker, S. T.; Phillips, E.; Perry, V. H.; Mann, D. A.; Barton, C. H.
• Is Part Of: Biochemical Society transactions. Volume 30:Number 4(2002)
• Page Start: 774
• Page End: 777
• Publication Date: 2002-08
• Subjects: initiator element -- macrophage -- repression; Nramp, natural resistance-associated macrophage protein -- CAT, chloramphenicol acetyltransferase -- miz-l, Myc-interacting zinc finger protein I; Biochemistry -- Congresses; 572
• DOI: 10.1042/bst0300774
• Languages: English
• ISSNs: 0300-5127

Abstract

Abstract : The Nrampl (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. Nrampl 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 Nrampl regulation was evaluated. Co-transfection studies show that c-Myc represses Nrampl promoter function. Five non-canonical Myc-max binding sites (E-box) identified within the Nrampl 5′-flanking sequence are not responsible for the inhibitory effects of c-Myc on Nrampl expression. An initiator(s) adjacent to the transcriptioninitiation site is a candidate for the inhibition observed. Results are consistent with a role for Nrampl removing iron from the cytosol and antagonizing c-Myc function.