Goessling L S, Mascotti D P, Thach R E
Department of Biology, Washington University, St. Louis, Missouri 63130, USA.
J Biol Chem. 1998 May 15;273(20):12555-7. doi: 10.1074/jbc.273.20.12555.
Iron-regulatory proteins (IRPs) recognize and bind to specific RNA structures called iron-responsive elements. Mediation of these binding interactions by iron and iron-containing compounds regulates several post-transcriptional events relevant to iron metabolism. There are two known IRPs, IRP1 and IRP2, both of which can respond to iron fluxes in the cell. There is ample evidence that IRP1 is converted by iron to cytoplasmic aconitase in vivo. It has also been shown that, under certain conditions, a significant fraction of IRP1 is degraded in cells exposed to iron or heme. Studies have shown that the degradation of IRP1 that is induced by iron can be inhibited by either desferrioxamine mesylate (an iron chelator) or succinyl acetone (an inhibitor of heme synthesis), whereas the degradation induced by heme cannot. This suggests that heme rather than iron is responsible for this degradation. Several laboratories have shown that IRP2 is also degraded in cells treated with iron salts. We now show evidence suggesting that this IRP2 degradation may be mediated by heme. Thus, in experiments analogous to those used previously to study IRP1, we find that IRP2 is degraded in rabbit fibroblast cells exposed to heme or iron salts. However, as shown earlier with IRP1, both desferrioxamine mesylate and succinyl acetone will inhibit the degradation of IRP2 induced by iron but not that induced by heme.
铁调节蛋白（IRPs）识别并结合特定的RNA结构，即铁反应元件。铁和含铁化合物介导的这些结合相互作用调节了与铁代谢相关的几个转录后事件。已知有两种IRP，即IRP1和IRP2，它们都能对细胞内的铁流量作出反应。有充分证据表明，IRP1在体内会被铁转化为细胞质乌头酸酶。研究还表明，在某些条件下，暴露于铁或血红素的细胞中，相当一部分IRP1会被降解。研究表明，铁诱导的IRP1降解可被甲磺酸去铁胺（一种铁螯合剂）或琥珀酰丙酮（一种血红素合成抑制剂）抑制，而血红素诱导的降解则不能。这表明是血红素而非铁导致了这种降解。几个实验室已经表明，在用铁盐处理的细胞中，IRP2也会被降解。我们现在提供的证据表明，这种IRP2降解可能是由血红素介导的。因此，在类似于先前用于研究IRP1的实验中，我们发现暴露于血红素或铁盐的兔成纤维细胞中的IRP2会被降解。然而，正如之前对IRP1的研究所示，甲磺酸去铁胺和琥珀酰丙酮都能抑制铁诱导的IRP2降解，但不能抑制血红素诱导的降解。
