FIG. 8.

Equilibrium between Gadd34/PP1c and HRI controls hemoglobin production. Abundant hemin prevents induction of HRI kinase activity above its basal role. Normocytic, normochromic erythrocytes arise from the balanced activities of Gadd34/PP1c and HRI kinase (center). Lack of HRI kinase (HRI-null) shifts the equilibrium toward unphosphorylated eIF2α(S51), favoring translation initiation and resulting in macrocytic, hyperchromic erythrocytes (left). Lack of Gadd34 (Gadd34-null), and hence failed recruitment of PP1c, shifts the equilibrium toward p-eIF2α(S51), favoring translation initiation attenuation and resulting in microcytic, hypochromic erythrocytes (right).