Disruption of Cellular Translational Control by a Viral Truncated Eukaryotic Translation Initiation Factor 2α Kinase Homolog

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 8; pp. 4164 - 4169
• Main Authors: Dever, Thomas E., Sripriya, Rajaraman, McLachlin, Jeanne R., Lu, Jingfang, Fabian, John R., Kimball, Scot R., Miller, Lois K.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of the United States of America 14-04-1998; National Acad Sciences; The National Academy of Sciences
• Subjects: Amino acids; Baculoviridae; Biological Sciences; Cell lines; Gels; Insect viruses; Phosphorylation; Plasmids; Proteins; Viruses; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.8.4164

Phosphorylation of eukaryotic translation initiation factor 2α (eIF2α ) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2α kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2α phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA-regulated (PKR), an eIF2α kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.