Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper.

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TitleInhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper.
Publication TypeJournal Article
Year of Publication2003
AuthorsColón-Ramos, DA, Irusta, PM, Gan, EC, Olson, MR, Song, J, Morimoto, RI, Elliott, RM, Lombard, M, Hollingsworth, R, Hardwick, MJ, Smith, GK, Kornbluth, S
JournalMol Biol Cell
Volume14
Issue10
Pagination4162-72
Date Published2003 Oct
ISSN1059-1524
KeywordsAmino Acid Motifs, Amino Acid Sequence, Animals, Apoptosis, Bunyaviridae, Carrier Proteins, Caspases, Cells, Cultured, Cytochromes c, Drosophila melanogaster, Drosophila Proteins, HSP70 Heat-Shock Proteins, Mitochondria, Molecular Sequence Data, Protein Biosynthesis, Recombinant Proteins, Sequence Homology, Amino Acid, Viral Nonstructural Proteins, Xenopus Proteins
Abstract

Members of the California serogroup of bunyaviruses (family Bunyaviridae) are the leading cause of pediatric viral encephalitis in North America. Significant cell death is observed as part of the infection pathology. We now report that a Bunyaviral nonstructural protein termed NSs shows sequence similarity to Reaper, a proapoptotic protein from Drosophila. Although NSs proteins lack the Reaper N-terminal motif critical for IAP inhibition, they do retain other functions of Reaper that map to conserved C-terminal regions. Like Reaper, NSs proteins induce mitochondrial cytochrome c release and caspase activation in cell-free extracts and promote neuronal apoptosis and mortality in a mouse model. Independent of caspase activation, Bunyavirus NSs proteins also share with Reaper the ability to directly inhibit cellular protein translation. We have found that the shared capacity to inhibit translation and induce apoptosis resides in common sequence motifs present in both Reaper and NSs proteins. Data presented here suggest that NSs induce apoptosis through a mechanism similar to that used by Reaper, as both proteins bind to an apoptotic regulator called Scythe and can relieve Scythe inhibition of Hsp70. Thus, bunyavirus NSs proteins have multiple Reaper-like functions that likely contribute to viral pathogenesis by promoting cell death and/or inhibiting cellular translation.

DOI10.1091/mbc.E03-03-0139
Alternate JournalMol. Biol. Cell
PubMed ID14517326