title: Direct suppression of Stat1 function during adenoviral infection.
abstract: The action of adenoviral E1A oncoprotein on host immune-response genes has been attributed to interaction with p300/CBP-type transcriptional coactivators in competition with endogenous transcription factors such as signal transducer and activator of transcription (STAT) proteins. However, we show that mutant forms of E1A that no longer bind p300/CBP can still interact directly with Stat1 (via E1A N-terminal and Stat1 C-terminal residues) and block IFNgamma-driven, Stat1-dependent gene activation and consequent function during early-phase infection in the natural host cell. The results provide a distinct and more specific mechanism for E1A-mediated immune suppression and an alternative model of IFNgamma-driven enhanceosome formation that may allow for other adaptors (in addition to p300/CBP) to link Stat1 to the basal transcription complex.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: D C
authors.initials: DC
authors.lastname: Look
authors.forename: W T
authors.initials: WT
authors.lastname: Roswit
authors.forename: A G
authors.initials: AG
authors.lastname: Frick
authors.forename: Y
authors.initials: Y
authors.lastname: Gris-Alevy
authors.forename: D M
authors.initials: DM
authors.lastname: Dickhaus
authors.forename: M J
authors.initials: MJ
authors.lastname: Walter
authors.forename: M J
authors.initials: MJ
authors.lastname: Holtzman
mesh_terms: D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism*; D000260:Adenoviruses, Human / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism; D050794:STAT1 Transcription Factor; D013601:T-Lymphocytes / Q000187:drug effects; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D007371:Interferon-gamma