Regulation of hemoglobin synthesis and proliferation of differentiating erythroid cells by heme-regulated eIF-2α kinase
| العنوان: | Regulation of hemoglobin synthesis and proliferation of differentiating erythroid cells by heme-regulated eIF-2α kinase |
|---|---|
| المؤلفون: | John S. Crosby, Peter J. Chefalo, Irene Yeh, Shong Ying, Irving M. London, Philippe Leboulch, Jane-Jane Chen |
| المصدر: | Blood. 96:3241-3248 |
| بيانات النشر: | American Society of Hematology, 2000. |
| سنة النشر: | 2000 |
| مصطلحات موضوعية: | Immunology, Cell Biology, Hematology, Biochemistry |
| الوصف: | Protein synthesis in reticulocytes depends on the availability of heme. In heme deficiency, inhibition of protein synthesis correlates with the activation of heme-regulated eIF-2α kinase (HRI), which blocks the initiation of protein synthesis by phosphorylating eIF-2α. HRI is a hemoprotein with 2 distinct heme-binding domains. Heme negatively regulates HRI activity by binding directly to HRI. To further study the physiological function of HRI, the wild-type (Wt) HRI and dominant-negative inactive mutants of HRI were expressed by retrovirus-mediated transfer in both non-erythroid NIH 3T3 and mouse erythroleukemic (MEL) cells. Expression of Wt HRI in 3T3 cells resulted in the inhibition of protein synthesis, a loss of proliferation, and eventually cell death. Expression of the inactive HRI mutants had no apparent effect on the growth characteristics or morphology of NIH 3T3 cells. In contrast, expression of 3 dominant-negative inactive mutants of HRI in MEL cells resulted in increased hemoglobin production and increased proliferative capacity of these cells upon dimethyl-sulfoxide induction of erythroid differentiation. These results directly demonstrate the importance of HRI in the regulation of protein synthesis in immature erythroid cells and suggest a role of HRI in the regulation of the numbers of matured erythroid cells. |
| تدمد: | 1528-0020 0006-4971 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::b6ca7df6f6fd2ba08ff97d2939c410b1 https://doi.org/10.1182/blood.v96.9.3241.h8003241_3241_3248 |
| رقم الأكسشن: | edsair.doi...........b6ca7df6f6fd2ba08ff97d2939c410b1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15280020 00064971 |
|---|