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c-Myc represses the murine Nramp1 promoter

Lookup NU author(s): Professor Derek Mann

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Abstract

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.


Publication metadata

Author(s): Mann DA; Bowen H; Biggs TE; Baker ST; Phillips E; Perry VH; Barton CH

Publication type: Article

Publication status: Published

Journal: Transactions of the Biochemical Society

Year: 2002

Volume: 30

Issue: 4

Pages: 774-777

ISSN (print): 0300-5127

ISSN (electronic): 1470-8752

Publisher: Portland Press Ltd.

URL: http://dx.doi.org/10.1042/BST0300774

DOI: 10.1042/BST0300774


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