Involvement of heme in the degradation of iron-regulatory protein 2.
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.
Goessling
L S
LS
Department of Biology, Washington University, St. Louis, Missouri 63130, USA.
Mascotti
D P
DP
Thach
R E
RE
D000818:Animals; D002460:Cell Line; D003676:Deferoxamine / Q000378:metabolism; D006418:Heme / Q000378:metabolism*; D006868:Hydrolysis; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011817:Rabbits
D007502:Iron Chelating Agents; D035925:Iron-Regulatory Proteins; D007506:Iron-Sulfur Proteins; D016601:RNA-Binding Proteins; D006418:Heme; D007501:Iron; D035941:Iron Regulatory Protein 1; D035942:Iron Regulatory Protein 2; D003676:Deferoxamine