| First Author | Meyron-Holtz EG | Year | 2004 |
| Journal | Science | Volume | 306 |
| Issue | 5704 | Pages | 2087-90 |
| PubMed ID | 15604406 | Mgi Jnum | J:94824 |
| Mgi Id | MGI:3521564 | Doi | 10.1126/science.1103786 |
| Citation | Meyron-Holtz EG, et al. (2004) Mammalian tissue oxygen levels modulate iron-regulatory protein activities in vivo. Science 306(5704):2087-90 |
| abstractText | The iron-regulatory proteins (IRPs) posttranscriptionally regulate expression of transferrin receptor, ferritin, and other iron metabolism proteins. Although both IRPs can regulate expression of the same target genes, IRP2-/- mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1-/- mice are spared. We found that IRP2-/- cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiological tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiological oxygen tensions. |
