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

Publication ,  Journal Article
Colón-Ramos, DA; Irusta, PM; Gan, EC; Olson, MR; Song, J; Morimoto, RI; Elliott, RM; Lombard, M; Hollingsworth, R; Hardwick, JM; Smith, GK ...
Published in: Molecular biology of the cell
October 2003

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.

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Published In

Molecular biology of the cell

DOI

EISSN

1939-4586

ISSN

1059-1524

Publication Date

October 2003

Volume

14

Issue

10

Start / End Page

4162 / 4172

Related Subject Headings

  • Xenopus Proteins
  • Viral Nonstructural Proteins
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • Protein Biosynthesis
  • Molecular Sequence Data
  • Molecular Chaperones
  • Mitochondria
  • HSP70 Heat-Shock Proteins
  • Drosophila melanogaster
 

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Colón-Ramos, D. A., Irusta, P. M., Gan, E. C., Olson, M. R., Song, J., Morimoto, R. I., … Kornbluth, S. (2003). Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper. Molecular Biology of the Cell, 14(10), 4162–4172. https://doi.org/10.1091/mbc.e03-03-0139
Colón-Ramos, Daniel A., Pablo M. Irusta, Eugene C. Gan, Michael R. Olson, Jaewhan Song, Richard I. Morimoto, Richard M. Elliott, et al. “Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper.Molecular Biology of the Cell 14, no. 10 (October 2003): 4162–72. https://doi.org/10.1091/mbc.e03-03-0139.
Colón-Ramos DA, Irusta PM, Gan EC, Olson MR, Song J, Morimoto RI, et al. Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper. Molecular biology of the cell. 2003 Oct;14(10):4162–72.
Colón-Ramos, Daniel A., et al. “Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper.Molecular Biology of the Cell, vol. 14, no. 10, Oct. 2003, pp. 4162–72. Epmc, doi:10.1091/mbc.e03-03-0139.
Colón-Ramos DA, Irusta PM, Gan EC, Olson MR, Song J, Morimoto RI, Elliott RM, Lombard M, Hollingsworth R, Hardwick JM, Smith GK, Kornbluth S. Inhibition of translation and induction of apoptosis by Bunyaviral nonstructural proteins bearing sequence similarity to reaper. Molecular biology of the cell. 2003 Oct;14(10):4162–4172.

Published In

Molecular biology of the cell

DOI

EISSN

1939-4586

ISSN

1059-1524

Publication Date

October 2003

Volume

14

Issue

10

Start / End Page

4162 / 4172

Related Subject Headings

  • Xenopus Proteins
  • Viral Nonstructural Proteins
  • Sequence Homology, Amino Acid
  • Recombinant Proteins
  • Protein Biosynthesis
  • Molecular Sequence Data
  • Molecular Chaperones
  • Mitochondria
  • HSP70 Heat-Shock Proteins
  • Drosophila melanogaster