PIAS1 selectively inhibits interferon-inducible genes and is important in innate immunity.
Interferon (IFN) activates the signal transducer and activator of transcription (STAT) pathway to regulate immune responses. The protein inhibitor of activated STAT (PIAS) family has been suggested to negatively regulate STAT signaling. To understand the physiological function of PIAS1, we generated Pias1(-/-) mice. Using PIAS1-deficient cells, we show that PIAS1 selectively regulates a subset of IFN-gamma- or IFN-beta-inducible genes by interfering with the recruitment of STAT1 to the gene promoter. The antiviral activity of IFN-gamma or IFN-beta was consistently enhanced by Pias1 disruption. Pias1(-/-) mice showed increased protection against pathogenic infection. Our data indicate that PIAS1 is a physiologically important negative regulator of STAT1 and suggest that PIAS1 is critical for the IFN-gamma- or IFN-beta-mediated innate immune responses.
Division of Hematology-Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Bin
B
Liu
Sheldon
S
Mink
Kelly A
KA
Wong
Natalie
N
Stein
Crescent
C
Getman
Paul W
PW
Dempsey
Hong
H
Wu
Ke
K
Shuai
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D006566:Herpesviridae Infections / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000276:immunology; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018353:Rhabdoviridae Infections / Q000276:immunology; D018144:Rhadinovirus / Q000276:immunology; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D004268:DNA-Binding Proteins; C494211:Pias1 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D007372:Interferons