Differential effect of Mn2+ on the hemin-controlled translational repressor and the double-stranded RNA-activated inhibitor - PubMed (original) (raw)

Differential effect of Mn2+ on the hemin-controlled translational repressor and the double-stranded RNA-activated inhibitor

M Gross et al. Biochim Biophys Acta. 1983.

Abstract

The inhibition of protein synthesis that occurs when rabbit reticulocyte lysate is incubated in the absence of hemin is due to the activation of a protein kinase termed the hemin-controlled translational repressor, and that occurring when reticulocyte lysate is incubated with a low level of double-stranded RNA is mediated by the activation of a separate protein kinase termed the double-stranded RNA-activated inhibitor. Both the hemin-controlled translational repressor and the double-stranded RNA-activated inhibitor act by phosphorylating the Mr = 35,000 (alpha) subunit of eIF-2. MnCl2 (0.5 mM) partly reverses the inhibition of protein synthesis produced by hemin deficiency but not that induced by double-stranded RNA. In addition, Mn2+ reverses the inhibition of binding of [35S]Met-tRNAf to reticulocyte ribosomal components, isolated on Sepharose 6B, produced by the hemin-controlled translational repressor but not by the double-stranded RNA-activated inhibitor. The effect of Mn2+ is mediated at the level of activation and eIF-2 alpha kinase activity of these two regulatory protein kinases. Specifically, Mn2+ inhibits activation of the hemin-controlled translational repressor in the absence of hemin and the phosphorylation of eIF-2 alpha by pre-activated translational repressor. In contrast, the phosphorylation of eIF-2 alpha by the double-stranded RNA-activated inhibitor is not suppressed by Mn2+, and the activation and autophosphorylation of this inhibitor is enhanced by Mn2+. Finally, while the activation and inactivation of the hemin-controlled translational repressor does not appear to be mediated by autophosphorylation and dephosphorylation, the activation of the double-stranded RNA-activated inhibitor does appear to require autophosphorylation.

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Differential effect of Mn2+ on the hemin-controlled translational repressor and the double-stranded RNA-activated inhibitor - PubMed (original) (raw)