Transcriptional control of Nramp1: a paradigm for the repressive action of c-Myc.
Slc11a1/Nramp1 (solute carrier family 11 member a1/murine natural resistance-associated macrophage protein 1 gene) encodes a divalent cation transporter that resides within lysosomes/late endosomes of macrophages. Nramp1 modulates the cellular distribution of divalent cations in response to cell activation by intracellular pathogens. Nramp1 expression is repressed and activated by the proto-oncogene c-Myc and Miz-1 (c-Myc-interacting zinc finger protein 1) respectively. Here we demonstrate, using a c-Myc mutant (V394D, Val(394)-->Asp) that is incapable of binding Miz-1, that c-Myc repression of Nramp1 transcription is dependent on its interaction with Miz-1. An oligo pull-down assay demonstrates specific binding of recombinant Miz-1 to the Nramp1 Miz-1-binding site or initiator element(s), and Miz-1-dependent c-Myc recruitment.
Lapham
A S
AS
Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, U.K.
Phillips
E S
ES
Barton
C H
CH
D001483:Base Sequence; D027682:Cation Transport Proteins / Q000235:genetics*; D002413:Cations, Divalent; D002468:Cell Physiological Phenomena; D016259:Genes, myc; D005822:Genetic Vectors; D008957:Models, Genetic; D015183:Restriction Mapping; D014158:Transcription, Genetic; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D002413:Cations, Divalent; D000099173:Natural Resistance-associated Macrophage Protein 1