Activation of interferon regulatory factor 3 in response to DNA-damaging agents.
Genotoxic stress triggers signal transduction pathways that mediate either the protection or apoptosis of affected cells. The interferon regulatory factors (IRFs) are involved in a wide range of host defense mechanisms against environmental stresses. Treatment with DNA-damaging agents, including doxorubicin and UV radiation, caused phosphorylation of the IRF3 transcription factor. Phosphorylation of IRF3 induced its interaction with the transcriptional co-activator cAMP-response element binding protein-binding protein. Furthermore, genotoxic stress-induced phosphorylation of IRF3 resulted in its movement from the cytoplasm to the nucleus, where it activated transcription from its binding site. These observations suggest that IRF3 plays a role in the defensive responses induced by genotoxic stress.
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National Creative Research Initiative Center for Genetic Reprogramming, Institute for Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea. TK_Kim@hms.harvard.edu
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D019943:Amino Acid Substitution; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D004317:Doxorubicin / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D050838:Interferon Regulatory Factor-3; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D014162:Transfection; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; D011994:Recombinant Proteins; D014157:Transcription Factors; D004317:Doxorubicin