Regulation of IRF2 transcriptional activity by its sumoylation.
IRFs constitute a family of transcription factors involved in IFN signaling and in the development and differentiation of the immune system. IRFs activities are regulated at transcriptional level (such as IRF1) and post-translational modifications (such as IRF3 and IRF7). Here we show that IRF2 interacts with the SUMO-E3 ligase PIASy and is sumoylated in vivo. Mutagenesis analysis suggests that IRF2 contains three sumoylation sites. Sumoylation of IRF2 has no significant effects on its nuclear localization and DNA-binding activity, but increases its ability to inhibit IRF1 transcriptional activity and decreases its ability to activate the ISRE and H4 promoters. Our findings suggest that sumoylation of IRF2 regulates its transcriptional activities.
Han
Ke-Jun
KJ
Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Jiang
Ling
L
Shu
Hong-Bing
HB
D002384:Catalysis; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D006655:Histone Deacetylases; D006657:Histones / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation; D050836:Interferon Regulatory Factor-2 / Q000235:genetics / Q000378:metabolism*; D016296:Mutagenesis; D000075223:Poly-ADP-Ribose Binding Proteins; D011401:Promoter Regions, Genetic; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020218:Response Elements; D025842:SUMO-1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D006657:Histones; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; C485891:PIAS4 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D044767:Ubiquitin-Protein Ligases; D006655:Histone Deacetylases