First Author | Hausmann A | Year | 2011 |
Journal | FEBS Lett | Volume | 585 |
Issue | 4 | Pages | 687-92 |
PubMed ID | 21281640 | Mgi Jnum | J:169088 |
Mgi Id | MGI:4939841 | Doi | 10.1016/j.febslet.2011.01.036 |
Citation | Hausmann A, et al. (2011) Redox control of iron regulatory protein 2 stability. FEBS Lett 585(4):687-92 |
abstractText | Iron regulatory protein 2 (IRP2) is a critical switch for cellular and systemic iron homeostasis. In iron-deficient or hypoxic cells, IRP2 binds to mRNAs containing iron responsive elements (IREs) and regulates their expression. Iron promotes proteasomal degradation of IRP2 via the F-box protein FBXL5. Here, we explored the effects of oxygen and cellular redox status on IRP2 stability. We show that iron-dependent decay of tetracycline-inducible IRP2 proceeds efficiently under mild hypoxic conditions (3% oxygen) but is compromised in severe hypoxia (0.1% oxygen). A treatment of cells with exogenous H(2)O(2) protects IRP2 against iron and increases its IRE-binding activity. IRP2 is also stabilized during menadione-induced oxidative stress. These data demonstrate that the degradation of IRP2 in iron-replete cells is not only oxygen-dependent but also sensitive to redox perturbations. |