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Translation Initiation Control by Heme-Regulated Eukaryotic Initiation Factor 2α Kinase in Erythroid Cells under Cytoplasmic Stresses
- Source :
- Molecular and Cellular Biology. 21:7971-7980
- Publication Year :
- 2001
- Publisher :
- Informa UK Limited, 2001.
-
Abstract
- Cytoplasmic stresses, including heat shock, osmotic stress, and oxidative stress, cause rapid inhibition of protein synthesis in cells through phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) by eIF2alpha kinases. We have investigated the role of heme-regulated inhibitor (HRI), a heme-regulated eIF2alpha kinase, in stress responses of erythroid cells. We have demonstrated that HRI in reticulocytes and fetal liver nucleated erythroid progenitors is activated by oxidative stress induced by arsenite, heat shock, and osmotic stress but not by endoplasmic reticulum stress or nutrient starvation. While autophosphorylation is essential for the activation of HRI, the phosphorylation status of HRI activated by different stresses is different. The contributions of HRI in various stress responses were assessed with the aid of HRI-null reticulocytes and fetal liver erythroid cells. HRI is the only eIF2alpha kinase activated by arsenite in erythroid cells, since HRI-null cells do not induce eIF2alpha phosphorylation upon arsenite treatment. HRI is also the major eIF2alpha kinase responsible for the increased eIF2alpha phosphorylation upon heat shock in erythroid cells. Activation of HRI by these stresses is independent of heme and requires the presence of intact cells. Both hsp90 and hsc70 are necessary for all stress-induced HRI activation. However, reactive oxygen species are involved only in HRI activation by arsenite. Our results provide evidence for a novel function of HRI in stress responses other than heme deficiency.
- Subjects :
- Cytoplasm
Reticulocytes
Arsenites
Eukaryotic Initiation Factor-2
Gene Expression
Cell Separation
Biology
Endoplasmic Reticulum
Mice
eIF-2 Kinase
Osmotic Pressure
Stress, Physiological
Eukaryotic initiation factor
Animals
HSP70 Heat-Shock Proteins
HSP90 Heat-Shock Proteins
Phosphorylation
Heat shock
Molecular Biology
Erythroid Precursor Cells
Mice, Knockout
EIF-2 kinase
Endoplasmic reticulum
Autophosphorylation
HSC70 Heat-Shock Proteins
Cell Biology
Hsp90
Cell biology
Enzyme Activation
Oxidative Stress
Liver
Biochemistry
Protein Biosynthesis
biology.protein
Reactive Oxygen Species
Heat-Shock Response
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....b813e0bb96d6fa0a01b6478dee1fdccb