PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1.
Interferon regulatory factor-1 (IRF-1) is a transcriptional activator that is involved in interferon response, regulation of cell growth and oncogenesis. To try to identify the molecules that regulate the function of IRF-1, we performed yeast two-hybrid screening and isolated protein inhibitor of activated STAT3 (PIAS3) as an IRF-1-binding protein. This protein was also found to bind with small ubiquitin-related modifier-1 (SUMO-1) and ubiquitin-conjugating enzyme 9, an E2 in the SUMO-1-conjugating system. Co-expression of PIAS3 induced SUMO-1 modification of IRF-1 in a RING finger domain-dependent manner and also repressed transcriptional activity of IRF-1. Thus, PIAS3 functions as a SUMO-1 ligase for IRF-1 and also as a repressor of IRF-1 transcriptional activity.
Nakagawa
Koji
K
Department of Biochemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Yokosawa
Hideyoshi
H
D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D006801:Humans; D050856:Interferon Regulatory Factor-1; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics*; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D047908:Intracellular Signaling Peptides and Proteins; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; C109279:Pias3 protein, mouse; D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein