Promyelocytic leukemia zinc finger protein regulates interferon-mediated innate immunity.
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.
Xu
Dakang
D
Monash Institute of Medical Research, Monash University, Melbourne, Australia.
Holko
Michelle
M
Sadler
Anthony J
AJ
Scott
Bernadette
B
Higashiyama
Shigeki
S
Berkofsky-Fessler
Windy
W
McConnell
Melanie J
MJ
Pandolfi
Pier Paolo
PP
Licht
Jonathan D
JD
Williams
Bryan R G
BR
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
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