Iron-regulatory proteins limit hypoxia-inducible factor-2α expression in iron deficiency

被引：245
作者：
Sanchez, Mayka
Galy, Bruno
Muckenthaler, Martina U.
Hentze, Matthias W.
机构：
[1] Mol Med Partnership Unit, D-69120 Heidelberg, Germany
[2] European Mol Biol Lab, D-69117 Heidelberg, Germany
[3] Univ Heidelberg, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany
来源：
NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2007年 / 14卷 / 05期
关键词：
D O I：
10.1038/nsmb1222
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Hypoxia stimulates erythropoiesis, the major iron-utilization pathway. We report the discovery of a conserved, functional iron-responsive element (IRE) in the 5' untranslated region of the messenger RNA encoding endothelial PAS domain protein-1, EPAS1 (also called hypoxia- inducible factor-2a, HIF2a). Via this IRE, iron regulatory protein binding controls EPAS1 mRNA translation in response to cellular iron availability. Our results uncover a regulatory link that permits feedback control between iron availability and the expression of a key transcription factor promoting iron utilization. They also show that an IRE that is structurally distinct from, for example, the ferritin mRNA IRE and that has been missed by in silico approaches, can mediate mechanistically similar responses.
引用
收藏
页码：420 / 426
页数：7
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