Regulation of Protein Synthesis by the Heme-regulated Eif2alpha Kinase: Relevance to Anemias.
From: Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences and Technology (HST), MIT, Cambridge, MA 02139, USA. j-jchen@mit.edu
Blood
- Publish Date: Apr 2007
- ISSN: 0006-4971
- Volume: 109
- Issue: 7
- Pages: 2693-9
- Medium: Print
- Language: English
- Citation (JAMA): Chen Jane-Jane, et al. Regulation of Protein Synthesis by the Heme-regulated Eif2alpha Kinase: Relevance to Anemias.. Blood Apr 2007;109:2693-9
Abstract
During erythroid differentiation and maturation, it is critical that the 3 components of hemoglobin, alpha-globin, beta-globin, and heme, are made in proper stoichiometry to form stable hemoglobin. Heme-regulated translation mediated by the heme-regulated inhibitor kinase (HRI) provides one major mechanism that ensures balanced synthesis of globins and heme. HRI phosphorylates the alpha-subunit of eukaryotic translational initiation factor 2 (eLF2alpha) in heme deficiency, thereby inhibiting protein synthesis globally. In this manner, HRI serves as a feedback inhibitor of globin synthesis by sensing the intracellular concentration of heme through its heme-binding domains. HRI is essential not only for the translational regulation of globins, but also for the survival of erythroid precursors in iron deficiency. Recently, the protective function of HRI has also been demonstrated in murine models of erythropoietic protoporphyria and beta-thalassemia. In these 3 anemias, HRI is essential in determining red blood cell size, number, and hemoglobin content per cell. Translational regulation by HRI is critical to reduce excess synthesis of globin proteins or heme under nonoptimal disease states, and thus reduces the severity of these diseases. The protective role of HRI may be more common among red cell disorders.
Mesh Headings (Keywords): Anemia, Anemia, Hypochromic, Anemia, Iron-Deficiency, Animals, Blood Proteins, Enzyme Activation, Erythropoiesis, Heme, Humans, Mice, Models, Biological, Protoporphyria, Erythropoietic, Signal Transduction, beta-Thalassemia, eIF-2 Kinase
Check for Full Text / PubMed Unique Identifier (PMID): 17110456
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.