Regulation of hemoglobin synthesis and proliferation of differentiating erythroid cells by heme-regulated eIF-2α kinase

摘要: Protein synthesis in reticulocytes depends on the availability of heme. In heme deficiency, inhibition protein correlates with activation heme-regulated eIF-2α kinase (HRI), which blocks initiation by phosphorylating eIF-2α. HRI is a hemoprotein 2 distinct heme-binding domains. Heme negatively regulates activity binding directly to HRI. To further study physiological function HRI, wild-type (Wt) and dominant-negative inactive mutants were expressed retrovirus-mediated transfer both non-erythroid NIH 3T3 mouse erythroleukemic (MEL) cells. Expression Wt cells resulted synthesis, loss proliferation, eventually cell death. had no apparent effect growth characteristics or morphology contrast, expression 3 MEL increased hemoglobin production proliferative capacity these upon dimethyl-sulfoxide induction erythroid differentiation. These results demonstrate importance regulation immature suggest role numbers matured