Meta-Biol

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Protein kinase R (PKR, EIF2AK2) must dimerize and autophosphorylate in order to become activated and subsequently phosphorylate translation initiation factor eIF2 subunit alpha (eIF2alpha, EIF2S1) at S51 (Dar et al, 2005). As a result, eIF2 forms a complex with its own guanine nucleotide exchange factor, eIF2B, which inhibits the recycling of GTP for GDP on eIF2 (reviewed in Dever, 2002). eIF2alpha phosphorylation by PKR is sufficient to induce apoptosis (Scheuner et al, 2006). The resulting inhibition of protein translation is not complete, however, as many transcripts involved in the stress response are not affected or are even preferentially translated by mechanisms involving upstream open reading frames (uORFs) (reviewed by Wek, 2018).