Redox control of iron regulatory protein 2 stability.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Hausmann A,Lee J,Pantopoulos K

doi

10.1016/j.febslet.2011.01.036

subject

Has Abstract

pub_date

2011-02-18 00:00:00

pages

687-92

issue

4

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(11)00068-8

journal_volume

585

pub_type

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