title: Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity.
abstract: Interferons (IFNs) direct innate and acquired immune responses and, accordingly, are used therapeutically to treat a number of diseases, yet the diverse effects they elicit are not fully understood. Here, we identified the promyelocytic leukemia zinc finger (PLZF) protein as a previously unrecognized component of the IFN response. IFN stimulated an association of PLZF with promyelocytic leukemia protein (PML) and histone deacetylase 1 (HDAC1) to induce a decisive subset of IFN-stimulated genes (ISGs). Consequently, PLZF-deficient mice had a specific ISG expression defect and as a result were more susceptible to viral infection. This susceptibility correlated with a marked decrease in the expression of the key antiviral mediators and an impaired IFN-mediated induction of natural killer cell function. These results provide new insights into the regulatory mechanisms of IFN signaling and the induction of innate antiviral immunity.
authors.affiliation: Monash Institute of Medical Research, Monash University, Melbourne, Australia.
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
authors.forename: Michelle
authors.initials: M
authors.lastname: Holko
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Sadler
authors.forename: Bernadette
authors.initials: B
authors.lastname: Scott
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Windy
authors.initials: W
authors.lastname: Berkofsky-Fessler
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: McConnell
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Licht
authors.forename: Bryan R G
authors.initials: BR
authors.lastname: Williams
mesh_terms: D018354:Alphavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D000818:Animals; D045744:Cell Line, Tumor; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000821:virology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000235:genetics*; D016898:Interferon-alpha / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012672:Semliki forest virus / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; C513267:Zbtb16 protein, mouse; C484389:Hdac1 protein, mouse; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases