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- W1982904957 abstract "Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS). HHV-8 encodes an antiapoptotic viral Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (vFLIP/K13). The antiapoptotic activity of vFLIP/K13 has been attributed to an inhibition of caspase 8 activation and more recently to its capability to induce the expression of antiapoptotic proteins via activation of NF-kappaB. Our study provides the first proteome-wide analysis of the effect of vFLIP/K13 on cellular-protein expression. Using comparative proteome analysis, we identified manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant and an important antiapoptotic enzyme, as the protein most strongly upregulated by vFLIP/K13 in endothelial cells. MnSOD expression was also upregulated in endothelial cells upon infection with HHV-8. Microarray analysis confirmed that MnSOD is also upregulated at the RNA level, though the differential expression at the RNA level was much lower (5.6-fold) than at the protein level (25.1-fold). The induction of MnSOD expression was dependent on vFLIP/K13-mediated activation of NF-kappaB, occurred in a cell-intrinsic manner, and was correlated with decreased intracellular superoxide accumulation and increased resistance of endothelial cells to superoxide-induced death. The upregulation of MnSOD expression by vFLIP/K13 may support the survival of HHV-8-infected cells in the inflammatory microenvironment in KS." @default.
- W1982904957 created "2016-06-24" @default.
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- W1982904957 date "2009-01-15" @default.
- W1982904957 modified "2023-09-27" @default.
- W1982904957 title "Viral Inhibitor of Apoptosis vFLIP/K13 Protects Endothelial Cells against Superoxide-Induced Cell Death" @default.
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- W1982904957 doi "https://doi.org/10.1128/jvi.00629-08" @default.
- W1982904957 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2612377" @default.
- W1982904957 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18987137" @default.
- W1982904957 hasPublicationYear "2009" @default.