7a protein of severe acute respiratory syndrome coronavirus inhibits cellular protein synthesis and activates p38 mitogen-activated protein kinase.
It was recently shown that the 7a protein of severe acute respiratory syndrome coronavirus induces biochemical changes associated with apoptosis. In this study, the mechanism by which the 7a protein induces apoptosis was examined. The 7a protein was tested for the ability to inhibit cellular gene expression because several proapoptotic viral proteins with this function have previously been identified. 7a protein inhibited expression of luciferase from an mRNA construct that specifically measures translation, whereas inhibitors of transcription and nucleocytoplasmic transport did not. The inhibition of translation and other cellular processes of gene expression have been associated with the induction of a stress response in cells. Western blot analysis using phosphospecific antibodies indicated that 7a protein activated p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal protein kinase/stress-activated protein kinase. Taken together, these data indicate that the induction of apoptosis by the 7a protein may be related to its ability to inhibit cellular translation and activate p38 MAPK.
Kopecky-Bromberg
Sarah A
SA
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029-6574, USA.
Martinez-Sobrido
Luis
L
Palese
Peter
P
D017209:Apoptosis; D002460:Cell Line; D002477:Cells; D015536:Down-Regulation; D004789:Enzyme Activation; D015870:Gene Expression; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D014176:Protein Biosynthesis / Q000502:physiology*; D014763:Viral Matrix Proteins; D014764:Viral Proteins / Q000378:metabolism / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D008565:Membrane Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C488151:sars7a protein, SARS virus; D008156:Luciferases; D048051:p38 Mitogen-Activated Protein Kinases