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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 (eIF2α), 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...

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Detalles Bibliográficos
Autores principales: de la Cruz-Herrera, Carlos F., Baz-Martínez, Maite, Motiam, Ahmed El, Vidal, Santiago, Collado, Manuel, Vidal, Anxo, Rodríguez, Manuel S., Esteban, Mariano, Rivas, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656663/
https://www.ncbi.nlm.nih.gov/pubmed/29070839
http://dx.doi.org/10.1038/s41598-017-12777-7
Descripción
Sumario:Activated dsRNA-dependent serine/threonine kinase PKR phosphorylates the alpha subunit of eukaryotic initiation factor 2 (eIF2α), 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 eIF2α 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.