Abstract
DNA viruses have evolved elaborate mechanisms to overcome host antiviral defences. In adenovirus-infected cells, programmed cell death (apoptosis) induced by the cytokine tumour necrosis factor (TNF) is inhibited by several adenovirus-encoded proteins1,2,3. Occupation of the cell-surface receptor Fas, a member of the TNF-receptor superfamily that is expressed on most cell types, triggers apoptosis of that cell4,5,6. Here we show that the adenovirus RID (for receptor internalization and degradation) protein complex, which is an inhibitor of TNF-induced apoptosis2, mediates internalization of cell-surface Fas and its destruction inside lysosomes within the cell. Fas has not previously been shown to be internalized and then degraded. RID also mediates internalization of the receptor for epidermal growth factor7,8, but it does not affect the transferrin receptor or class I antigens of the major histocompatibility complex. Removal of Fas from the surface of adenovirus-infected cells expressing RID may allow infected cells to resist Fas-mediated cell death and thus promote their survival.
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Acknowledgements
We thank J. Freeman for help with the confocal microscopy, V. Dixit for the MCF7 and MCF7-Fas cell lines and for pcDNA-3-Fas, M. Green for the pMT2 vector, the ERp72 antiserum, and COS7 cells, M. Green for the DBP antiserum, M. Fukuda for LAMP1 antiserum, E. Harlow for the M73 mAb, C. Gugliemo for technical assistance, J. Mikes for preparation of the manuscript and figures, and C.Pollack for photography.
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Tollefson, A., Hermiston, T., Lichtenstein, D. et al. Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells. Nature 392, 726–730 (1998). https://doi.org/10.1038/33712
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DOI: https://doi.org/10.1038/33712
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