Phosphorylable tyrosine residue 162 in the double-stranded RNA-dependent kinase PKR modulates its interaction with SUMO.
Activated dsRNA-dependent serine/threonine kinase PKR phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2?), resulting in a shut-off of general translation, induction of apoptosis, and inhibition of virus replication. PKR can be activated by binding to dsRNA or cellular proteins such as PACT/RAX, or by its conjugation to ISG15 ... or SUMO. Here, we demonstrate that PKR also interacts with SUMO in a non-covalent manner. We identify the phosphorylable tyrosine residue 162 in PKR (Y162) as a modulator of the PKR-SUMO non-covalent interaction as well as of the PKR SUMOylation. Finally, we show that the efficient SUMO-mediated eIF2? phosphorylation and inhibition of protein synthesis induced by PKR in response to dsRNA depend on this residue. In summary, our data identify a new mechanism of regulation of PKR activity and reinforce the relevance of both, tyrosine phosphorylation and SUMO interaction in controlling the activity of PKR.
Mesh Terms:
Animals, Apoptosis, Enzyme Activation, HEK293 Cells, Humans, Mice, Mice, Knockout, Phosphorylation, Protein Binding, RNA, Double-Stranded, SUMO-1 Protein, Sumoylation, Tyrosine, eIF-2 Kinase
Animals, Apoptosis, Enzyme Activation, HEK293 Cells, Humans, Mice, Mice, Knockout, Phosphorylation, Protein Binding, RNA, Double-Stranded, SUMO-1 Protein, Sumoylation, Tyrosine, eIF-2 Kinase
Sci Rep
Date: Dec. 25, 2016
PubMed ID: 29070839
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