PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis.
The TIR domain-containing adapter protein TRIP is critically involved in TLR3-induced IFN-beta production through activation of NF-kappaB and ISRE. In addition, TRIF also induces apoptosis when overexpressed in 293 cells. In this report, we demonstrate that PIASy, a member of the PIAS SUMO-ligase family, interacts with TRIP, IRF-3 and IRF-7. In reporter gene assays, PIASy dramatically inhibits TRIF-induced NF-kappaB, ISRE and IFN-beta activation but not TRIF-induced apoptosis. Furthermore, PIASy also inhibits IRF-3, IRF-7 and Sendai virus-induced ISRE activation. Our results suggest that PIASy is an inhibitor of TRIF-induced ISRE and NF-kappaB activation but not apoptosis.
Zhang
Jun
J
National Jewish Medical and Research Center, 1400 Jackson Street, k516c, Denver, CO 80206, USA.
Xu
Liang-Guo
LG
Han
Ke-Jun
KJ
Wei
Xudong
X
Shu
Hong-Bing
HB
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005799:Genes, Dominant; D017930:Genes, Reporter; D006801:Humans; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D000075223:Poly-ADP-Ribose Binding Proteins; D011233:Precipitin Tests; D011485:Protein Binding; D050828:Protein Inhibitors of Activated STAT; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D020218:Response Elements; D029082:Sendai virus / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; D016899:Interferon-beta; D007372:Interferons; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases; D016328:NF-kappa B; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D018124:Receptors, Tumor Necrosis Factor; D014157:Transcription Factors; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; C494232:IRF3 protein, human; C494234:IRF7 protein, human; C485891:PIAS4 protein, human; C476286:Ticam1 protein, mouse; C470409:TICAM1 protein, human