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- W1885451801 abstract "The inhibition of globin synthesis in hemin-deficient rabbit reticulocyte lysates is due to the activation of a hemin-controlled translational inhibitor (HCD that specifically phosphorylates eIF-2a. High concentrations of cAMP (5–10 mM) and GTP (1–2 mM) stimulated the globin synthesis in hemin-deficient lysates when these compounds were added at the initial stage of incubation. The mechanism of the stimulation by cAMP and GTP was studied using hemin-deficient lysates, the N-ethylmaleimide(NEM)-treated HCI-supplemented lysates and a partially purified initiation factor, eIF-2. As the stimulation of globin synthesis by these compounds must be due to the prevention of the inhibition of globin synthesis, or due to the restoration of globin synthesis, or both, the preventive and restorative effects of these compounds were examined. As for the preventive effect, it was observed that a) the activation of HCI in the postribosomal supernatant of reticulocytes was prevented by GTP, but not by cAMP, and b) cAMP and GTP inhibited the phosphorylation of eIF-2a in hemin-deficient lysates. As for the restorative effect of cAMP and GTP, it was observed that c) these compounds restored the globin synthesis and the binding of [35S]Met-tRNAf to the 40S ribosomal subunits, and promoted the dephosphorylation of eIF-2(aP), d) the rates of the restored synthesis of globin were lower than the control, and e) cAMP promoted the release of [3H]GDP from the eIF-2(aP).[3H]GDP complex and the formation of eIF-2(aP).eIF-2B complex. Finding (d) indicates that steps involved in the restorative effect of these compounds may not contribute to the stimulation of the globin synthesis in hemin-deficient lysates. The data on the preventive and restorative effects of cAMP and GTP showed that these compounds affected multiple steps. That is, cAMP inhibited the phosphorylation of eIF-2a and promoted both the release of GDP from eIF-2 and the" @default.
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- W1885451801 date "1985-05-01" @default.
- W1885451801 modified "2023-09-27" @default.
- W1885451801 title "Mechanism of Stimulation of Globin Synthesis by Adenosine-3',5'-Monophosphate and Guanosine 5'-Triphosphate in a Rabbit Reticulocyte Lysate System" @default.
- W1885451801 doi "https://doi.org/10.1093/oxfordjournals.jbchem.a135180" @default.
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