Meyron-Holtz Esther G, Ghosh Manik C, Rouault Tracey A
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Science. 2004 Dec 17;306(5704):2087-90. doi: 10.1126/science.1103786.
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.
铁调节蛋白（IRPs）在转录后水平调节转铁蛋白受体、铁蛋白及其他铁代谢蛋白的表达。尽管两种IRPs均可调节相同靶基因的表达，但IRP2基因敲除小鼠会显著地错误调节铁代谢并发生神经退行性变，而IRP1基因敲除小鼠则不会出现此现象。我们发现，IRP2基因敲除细胞在3%至6%氧气浓度下培养时会错误调节铁代谢，这一氧气浓度与生理组织浓度相当，而在21%氧气浓度下培养时则不会，21%氧气浓度会激活IRP1并使其能够替代IRP2。因此，IRP2在哺乳动物铁稳态调节中起主导作用，因为只有它能在生理氧张力下感知铁浓度并调节其RNA结合活性。
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