| First Author | Gunshin H | Year | 2001 |
| Journal | FEBS Lett | Volume | 509 |
| Issue | 2 | Pages | 309-16 |
| PubMed ID | 11741608 | Mgi Jnum | J:73309 |
| Mgi Id | MGI:2154867 | Doi | 10.1016/s0014-5793(01)03189-1 |
| Citation | Gunshin H, et al. (2001) Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett 509(2):309-16 |
| abstractText | The first step in intestinal iron absorption is mediated by the H(+)-coupled Fe(2+) transporter called divalent cation transporter 1/divalent metal ion transporter 1 (DCT1/DMT1) (also known as natural resistance-associated macrophage protein 2). DCT1/DMT1 mRNA levels in the duodenum strongly increase in response to iron depletion. To study the mechanism of iron-dependent DCT1/DMT1 mRNA regulation, we investigated the endogenous expression of DCT1/DMT1 mRNA in various cell types. We found that only the iron responsive element (IRE)-containing form, which corresponds to one of two splice forms of DCT1/DMT1, is responsive to iron treatment and this responsiveness was cell type specific. We also examined the interaction of the putative 3'-UTR IRE with iron responsive binding proteins (IRP1 and IRP2), and found that IRP1 binds to the DCT1/DMT1-IRE with higher affinity compared to IRP2. This differential binding of IRP1 and IRP2 was also reported for the IREs of transferrin receptors, erythroid 5-aminolevulinate synthase and mitochondrial aconitase. We propose that regulation of DCT1/DMT1 mRNA by iron involves post-transcriptional regulation through the binding of IRP1 to the transporter's IRE, as well as other as yet unknown factors. |
