title: Forced degradation of Fas inhibits apoptosis in adenovirus-infected cells.
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 proteins. 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 cell. Here we show that the adenovirus RID (for receptor internalization and degradation) protein complex, which is an inhibitor of TNF-induced apoptosis, 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 factor, 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, St Louis University School of Medicine, Missouri 63104-1004, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Tollefson
authors.forename: T W
authors.initials: TW
authors.lastname: Hermiston
authors.forename: D L
authors.initials: DL
authors.lastname: Lichtenstein
authors.forename: C F
authors.initials: CF
authors.lastname: Colle
authors.forename: R A
authors.initials: RA
authors.lastname: Tripp
authors.forename: T
authors.initials: T
authors.lastname: Dimitrov
authors.forename: K
authors.initials: K
authors.lastname: Toth
authors.forename: C E
authors.initials: CE
authors.lastname: Wells
authors.forename: P C
authors.initials: PC
authors.lastname: Doherty
authors.forename: W S
authors.initials: WS
authors.lastname: Wold
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D017501:Adenovirus E1B Proteins; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis; D002461:Cell Line, Transformed; D006801:Humans; D018942:Macrolides; D051379:Mice; D009154:Mutation; D014764:Viral Proteins; D019014:fas Receptor / Q000502:physiology*
chemical_list: D017501:Adenovirus E1B Proteins; D000900:Anti-Bacterial Agents; D018942:Macrolides; D014764:Viral Proteins; D019014:fas Receptor; C040929:bafilomycin A1