c-Myc represses and Miz-1 activates the murine natural resistance-associated protein 1 promoter
Bowen, H., Biggs, T.E., Phillips, E., Baker, S.T., Perry, V.H., Mann, D.A. and Barton, C.H. (2002) c-Myc represses and Miz-1 activates the murine natural resistance-associated protein 1 promoter. Journal of Biological Chemistry, 277, (38), 34997-35006. (doi:10.1074/jbc.M204232200).
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Description/Abstract
Iron is essential for growth, and impaired iron homoeostasis through a non-conserved mutation within murine Nramp1, also termed Slc11a1, contributes to susceptibility to infection. Nramp1 depletes the macrophage cytosol of iron, with effects on iron-regulated gene expression and iron-dependent processes. Wu and colleagues (Wu, K.-J., Polack, A., and Dalla-Favera, R. (1999) Science 283, 676-679) showed converse control of iron regulatory protein expression (IRP2) and H-ferritin by c-Myc, suggesting a role for c-Myc in enhancing cytoplasmic iron levels for growth. We investigated if c-Myc also regulates Nramp1 expression. We show an inverse correlation with cell growth, and in co-transfection experiments c-Myc represses the Nramp1 promoter. Within the Nramp1 promoter we identified six non-canonical E boxes, which are not important for c-Myc repression. By deletion analysis the repressor site maps to one or more initiator elements flanking the transcriptional initiation site. Co-transfections with the c-Myc interacting zinc finger protein (Miz-1) show that Miz-1 can overcome c-Myc repression of Nramp1, and, from a deletion construct lacking E box sites, Miz-1 activates the Nramp1 promoter. These studies reinforce the link between c-Myc and iron regulation and provide further evidence that c-Myc negatively regulates genes that decrease the iron content of the cytosol. The results provide further support for a divalent cation antiporter function for Nramp1.
| Item Type: | Article |
|---|---|
| ISSNs: | 0021-9258 (print) |
| Related URLs: | |
| Subjects: | R Medicine Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences University Structure - Pre August 2011 > School of Medicine > Infection, Inflammation and Repair |
| Item ID: | 26956 |
| Date Deposited: | 27 Apr 2006 |
| Last Modified: | 01 Jun 2011 02:03 |
| Contributors: | Bowen, H. (Author) Biggs, T.E. (Author) Phillips, E. (Author) Baker, S.T. (Author) Perry, V.H. (Author) Mann, D.A. (Author) Barton, C.H. (Author) |
| Date: | 2002 |
| Status: | Published |
| Contact Email Address: | CHB@soton.ac.uk |
| URI: | http://eprints.soton.ac.uk/id/eprint/26956 |
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