Heme-regulated eIF2α kinase modifies the phenotypic severity of murine models of erythropoietic protoporphyria and β-thalassemia

摘要: Heme-regulated eIF2α kinase (HRI) controls protein synthesis by phosphorylating the α-subunit of eukaryotic translational initiation factor 2 (eIF2α). In heme deficiency, HRI is essential for regulation α- and β-globins survival erythroid progenitors. also activated a number cytoplasmic stresses other than including oxidative stress heat shock. However, to date, has not been implicated in pathogenesis any known human disease or mouse phenotype. Here we report role models rbc disorders, namely erythropoietic protoporphyria (EPP) β-thalassemia. both cases, lack adversely modifies phenotype: deficiency exacerbates EPP renders β-thalassemia embryonically lethal. This study establishes protective function inherited diseases mice suggests that may be significant modifier many disorders humans. Our findings demonstrate could play critical clinical manifestation diseases.