Jaewhan Song

Publications (2)4.94 Total impact

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

  Daniel A Colón-Ramos, Pablo M Irusta, Eugene C Gan, Michael R Olson, Jaewhan Song, Richard I Morimoto, Richard M Elliott, Mark Lombard, Robert Hollingsworth, J Marie Hardwick, Gary K Smith, Sally Kornbluth
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  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.
  Molecular Biology of the Cell 11/2003; 14(10):4162-72. · 4.94 Impact Factor
• Chapter: Analysis of Molecular Chaperone Activities Using In Vitro and In Vivo Approaches

  Brian C. Freeman, Annamieke Michels, Jaewhan Song, Harm H. Kampinga, Richard I. Morimoto
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  ABSTRACT: Molecular chaperones function in a range of protein homeostatic events, including cotranslational protein folding, assembly and disassembly of protein complexes, and protein transport across membranes. Many molecular chaperones are also known as heat-shock proteins, which refers to their regulation by stress conditions as diverse as infection with viral and bacterial agents, exposure to transition heavy metals, heat shock, amino acid analogs, drugs, toxic chemicals, and pathophysiologic and disease states including oxidative stress, fever, inflammation, infection, myocardial stress and ischemia, neuro-degenerative diseases, aging, and cancer. The heat-shock response through the elevated expression of heat-shock proteins (Hsp’s) protects cells and tissues against the deleterious effects of stress. Pre-exposure to mild, nontoxic stresses such as lower heat-shock temperatures, and reduced levels of metals, arsenite, ethanol, or oxidants confers a transient resistance (thermotolerance) to a subsequent, otherwise lethal, exposure to stress. A common feature of most, if not all, stresses against which Hsp’s have protective capacity are effects on protein folding and protein aggregation.
  12/1999: pages 393-419;