The translation initiation factor eIF2{beta} is an interactor of protein phosphatase-1
Résumé
It is reasonably well understood how the initiation of translation is controlled by reversible phosphorylation of the translation initiation factors eIF2{alpha}, eIF2B{epsilon} and eIF4E. Other initiation factors, including eIF2{beta}, are also established phosphoproteins but the physiological impact of their phosphorylation is not known. Using a sequence homology search we found that the central region of the eukaryotic translation initiation factor eIF2{beta} contains a putative PP1-binding RVxF motif. The predicted eIF2{beta}-PP1 interaction was confirmed by PP1 binding and co-immunoprecipitation assays on cell lysates as well as with the purified components. Site-directed mutagenesis showed that eIF2{beta} contains, in addition to an RVxF-motif, at least one other PP1-binding site in its C-terminal half. eIF2{beta} functioned as an inhibitor for the dephosphorylation of glycogen phosphorylase and eIF2{alpha} (Ser51) by PP1, but did not affect the dephosphorylation of eIF2B{epsilon} (Ser464) by this phosphatase. Strikingly, eIF2{beta} emerged as an activator of its own dephosphorylation (Ser2, Ser218, Ser267) by associated PP1, since the substrate quality of eIF2{beta} was decreased by the mere mutation of its RVxF-motif. These data make eIF2{beta} an attractive in vivo candidate substrate for associated PP1. The overexpression of wild-type eIF2{beta} or eIF2{beta} with a mutated RVxF-motif did not differentially affect the rate of translation, indicating that the binding of PP1 is not rate-limiting for translation under basal circumstances.
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