Interferon regulatory factor-2 point mutations in human pancreatic tumors.
Interferon regulatory factor (IRF)-2, a member of the IRF family, is a transcription factor involved in the regulation of various interferon and virus-stimulated genes and other genes. For example, IRF-2 is an activator of the interferon (IFN)-gamma-inducible MHC class II transactivator (CIITA) type IV promoter. It cooperates with IRF-1 in the activation of the CIITA type IV promoter and can co-occupy the IRF-E of the promoter with IRF-1. In a previous study, we identified an inactivating point mutation in the DNA binding domain of IRF-2 expressed in a human pancreatic tumor cell line that does not express CIITA or MHC class II in response to IFN-gamma. To further assess the potential impact of IRF-2 mutations in tumorigenesis, we screened fresh pancreatic tumor explants and identified 2 IRF-2 point mutations in the 2 alleles of IRF-2 from a single tumor specimen. Both mutations occurred in the DNA binding domain of IRF-2. DNA binding assays demonstrated that the IRF-2 point mutations impaired IRF-2 DNA binding. The transactivation function of the mutant IRF-2s was similarly impaired. This is the first report of IRF-2 mutations in human tumor explants.
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Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
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D000483:Alleles; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050836:Interferon Regulatory Factor-2; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D017354:Point Mutation / Q000235:genetics*; D012097:Repressor Proteins; D017422:Sequence Analysis, DNA; D014157:Transcription Factors; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C494229:IRF2 protein, human; D050836:Interferon Regulatory Factor-2; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA