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Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-02-0433. This Article Full Text (PDF) All Versions of this Article: 2003-02-0433v1 102/9/3404    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Schneider, B. D Articles by Leibold, E. A Search for Related Content PubMed PubMed Citation Articles by Schneider, B. D Articles by Leibold, E. A Social Bookmarking                   What's this? Submitted February 10, 2003 Accepted June 24, 2003 Effects of iron regulatory protein regulation on iron homeostasis during hypoxia Brian D Schneider and Elizabeth A Leibold* Program in Human Molecular Biology and Genetics and the Departments of Oncological Sciences and Medicine, University of Utah, Salt Lake City, UT, USA * Corresponding author; email: betty.leibold{at}hmbg.utah.edu. Iron regulatory proteins (IRP1 and IRP2) are RNA-binding proteins that affect the translation and stabilization of specific mRNAs by binding to stem-loop structures known as iron responsive elements (IREs). IREs are found in the 5'-untranslated region (UTR) of ferritin (Ft) and mitochondrial aconitase (m-Aco) mRNAs, and in the 3'-UTR of transferrin receptor (TfR) and divalent metal transporter-1 (DMT1) mRNAs. Our previous studies show that besides iron, IRPs are regulated by hypoxia. Here we describe the consequences of IRP regulation and show that iron homeostasis is regulated in two phases during hypoxia: an early phase where IRP1 RNA-binding activity decreases and iron uptake and Ft synthesis increase, and a late phase where IRP2 RNA-binding activity increases and iron uptake and Ft synthesis decrease. The increase in iron uptake is independent of DMT1 and TfR, suggesting an unknown transporter. Unlike Ft, m-Aco is not regulated during hypoxia. During the late phase of hypoxia, IRP2 RNA-binding activity increases, becoming the dominant regulator responsible for decreasing Ft synthesis. During reoxygenation (ReO2), Ft protein increases concomitant with a decrease in IRP2 RNA-binding activity. The data suggest that the differential regulation of IRPs during hypoxia may be important for cellular adaptation to low oxygen tension. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. E. 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