Transcriptional control of Nramp 1: a paradigm for the repressive action of c-Myc
Transcriptional control of Nramp 1: 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, Val394Asp) 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.
1084-1086
Lapham, A.S.
124d8916-3c26-4d36-9678-e340016312bd
Phillips, E.S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Barton, C.H.
5dfb4e1a-d559-4b58-9036-31de1e6c9ad8
1 December 2004
Lapham, A.S.
124d8916-3c26-4d36-9678-e340016312bd
Phillips, E.S.
66ddd4cb-19a2-4d08-889b-12f418e6878b
Barton, C.H.
5dfb4e1a-d559-4b58-9036-31de1e6c9ad8
Lapham, A.S., Phillips, E.S. and Barton, C.H.
(2004)
Transcriptional control of Nramp 1: a paradigm for the repressive action of c-Myc.
Biochemical Society Transactions, 32 (6), .
Abstract
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, Val394Asp) 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.
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Published date: 1 December 2004
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Local EPrints ID: 56294
URI: http://eprints.soton.ac.uk/id/eprint/56294
ISSN: 0300-5127
PURE UUID: 518d5eb3-80bf-4407-adc6-456197120e15
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Date deposited: 06 Aug 2008
Last modified: 08 Jan 2022 02:51
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Author:
A.S. Lapham
Author:
E.S. Phillips
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