Publication Date:
2004-12-18
Description:
The iron-regulatory proteins (IRPs) posttranscriptionally regulate expression of transferrin receptor, ferritin, and other iron metabolism proteins. Although both IRPs can regulate expression of the same target genes, IRP2-/- mice significantly misregulate iron metabolism and develop neurodegeneration, whereas IRP1-/- mice are spared. We found that IRP2-/- cells misregulated iron metabolism when cultured in 3 to 6% oxygen, which is comparable to physiological tissue concentrations, but not in 21% oxygen, a concentration that activated IRP1 and allowed it to substitute for IRP2. Thus, IRP2 dominates regulation of mammalian iron homeostasis because it alone registers iron concentrations and modulates its RNA-binding activity at physiological oxygen tensions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meyron-Holtz, Esther G -- Ghosh, Manik C -- Rouault, Tracey A -- New York, N.Y. -- Science. 2004 Dec 17;306(5704):2087-90.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15604406" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Cells, Cultured
;
Ferritins/biosynthesis/metabolism
;
Gene Expression Regulation
;
Homeostasis
;
Iron/*metabolism
;
Iron Regulatory Protein 1/genetics/*metabolism
;
Iron Regulatory Protein 2/genetics/*metabolism
;
Lymphocytes/*metabolism
;
Macrophages/*metabolism
;
Mice
;
Oxidants/metabolism
;
Oxygen/*physiology
;
RNA/metabolism
;
Receptors, Transferrin/biosynthesis/metabolism
;
Response Elements
;
Spleen/cytology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
