Inhibition of protein synthesis initiation by oxidized glutathione: Activation of a protein kinase that phosphorylates the α subunit of eukaryotic initiation factor 2
- 1 September 1978
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 75 (9) , 4110-4114
- https://doi.org/10.1073/pnas.75.9.4110
Abstract
Oxidized glutathione (GSSG) (0.02-0.5 mM) inhibited [rabbit] reticulocyte lysates by a mechanism similar to that observed in heme deficiency. Incubation of hemin-supplemented postribosomal supernates with GSSG resulted in the activation of a translational inhibitor [I(GSSG)]. The activation of I(GSSG) was enhanced by the presence of an energy-regenerating system. The simultaneous addition of 1 mM dithiothreitol blocked the activation of the GSSG-induced inhibitor. Once inhibitor was formed, its activity was not affected by 1 mM dithiothreitol. GSSG-treated postribosomal supernates and partially purified preparations of I(GSSG) inhibited protein synthesis in hemin-supplemented lysates with biphasic kinetics. Inhibition by I(GSSF) was blocked by cyclic[c]AMP (2-10 mM) and is potentiated by ATP (2 mM). The inhibition was also blocked or reversed by eukaryotic initiation factor eIF-2. The activation of I(GSSG) was accompanied by an increased cAMP-independent protein kinase activity which phosphorylates the 38,000 dalton component (.alpha. subunit) of eIF-2; GSSG treatment of supernates did not alter the activity of the cAMP-independent protein kinase activity that phosphorylates the 49,000 dalton polypeptide component (.beta. subunit) of eIF-2. GSSG treatment of reticulocyte lysates apparently results in the activation of a protein kinase with inhibitory and phosphorylation properties similar to those of the heme-regulated cAMP-independent protein kinase which is activated in heme deficiency.Keywords
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