Ubc9-mediated sumoylation leads to transcriptional repression of IRF-1.
To characterize the regulatory mechanism of the interferon regulatory factor (IRF) family, we performed yeast two-hybrid screening with IRF-2 and isolated the small ubiquitin-related modifier (SUMO)-conjugating enzyme Ubc9, which also interacts with other IRF family members IRF-1 and ICSBP. Subsequent assays indicated that among the IRF family members, only IRF-1 ... interacts with SUMO-1 through its transcriptional activation domain. The interaction between IRF-1 and SUMO-1 was confirmed in vitro by GST pull-down assays and in vivo by co-localization assays. Furthermore, this interaction led to the Ubc9-mediated sumoylation of IRF-1 in vitro and in vivo. Transient transfection assays revealed that Ubc9 or SUMO inhibits the transcriptional activity of IRF-1 in a dose-dependent manner. Finally, Ubc9 and SUMO cooperate in the transcriptional repression of IRF-1. Taken together, these observations suggest that Ubc9 functions as a transcriptional repressor of IRF-1 by inducing sumoylation, and that this effect may be required for the physiological activity of IRF-1.
Mesh Terms:
Animals, Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Humans, Interferon Regulatory Factor-1, Interferon Regulatory Factor-2, Mice, NIH 3T3 Cells, Repressor Proteins, SUMO-1 Protein, Transcription, Genetic, Two-Hybrid System Techniques, Ubiquitin-Conjugating Enzymes
Animals, Cell Line, Tumor, Down-Regulation, Gene Expression Regulation, Humans, Interferon Regulatory Factor-1, Interferon Regulatory Factor-2, Mice, NIH 3T3 Cells, Repressor Proteins, SUMO-1 Protein, Transcription, Genetic, Two-Hybrid System Techniques, Ubiquitin-Conjugating Enzymes
Biochem. Biophys. Res. Commun.
Date: Dec. 19, 2008
PubMed ID: 18955028
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