NDLI: Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins.

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Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins.

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Iron-dependent oxidation, ubiquitination, and degradation of iron regulatory protein 2: implications for degradation of oxidized proteins.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Iwai, K. Lavaute, T. Wehr, N. B. Weissman, A. M. Levine, R. L. Drake, S. K. Minato, N. Rouault, T. A. Klausner, R. D.
Description	Author Affiliation: Iwai K ( Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA.);
Abstract	The ability of iron to catalyze formation of reactive oxygen species significantly contributes to its toxicity in cells and animals. Iron uptake and distribution is regulated tightly in mammalian cells, in part by iron regulatory protein 2 (IRP2), a protein that is degraded efficiently by the proteasome in iron-replete cells. Here, we demonstrate that IRP2 is oxidized and ubiquitinated in cells before degradation. Moreover, iron-dependent oxidation converts IRP2 into a substrate for ubiquitination in vitro. A regulatory pathway is described in which excess iron is sensed by its ability to catalyze site-specific oxidations in IRP2, oxidized IRP2 is ubiquitinated, and ubiquitinated IRP2 subsequently is degraded by the proteasome. Selective targeting and removal of oxidatively modified proteins may contribute to the turnover of many proteins that are degraded by the proteasome.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	9
Volume Number	95
Language	English
Publisher	National Academy of Sciences
Publisher Date	1998-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cysteine Endopeptidases Metabolism Iron-Sulfur Proteins Multienzyme Complexes RNA-Binding Proteins Animals COS Cells Cell-Free System Iron Regulatory Protein 2 Iron-Regulatory Proteins Oxidation-Reduction Proteasome Endopeptidase Complex Recombinant Proteins Ubiquitins Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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