Interferon-alpha activates binding of nuclear factors to a sequence element in the c-fos proto-oncogene 5'-flanking region.
Interferon-alpha (IFN-alpha) can regulate the expression of the c-fos proto-oncogene in different cell types. Here we show IFN-alpha-activated binding of murine and human fibroblast nuclear factors to a DNA sequence element located in the 5' upstream region (nucleotides -351/-337) of the c-fos gene. This element, like the conserved enhancer element, the IFN-stimulated response element (ISRE), that mediates transcriptional induction of IFN-alpha-inducible genes, also binds factors in response to platelet-derived growth factor (PDGF) and v-sis-conditioned medium (SCM). The IFN-inducible ISRE shares an 8-bp stretch of sequence homology with the IFN-responsive c-fos SCM element, and competes efficiently for binding of factors to the SCM. Protein-DNA cross-linking experiments with the SCM binding site identified an IFN-modulated nuclear protein of approximately 98 kD. This protein does not appear to be involved in transcription activation, since IFN-alpha failed to stimulate c-fos transcription in nuclear run-off assays, or the c-fos promoter in transient transcription assays of 3T3 fibroblasts. Our data nonetheless suggest the c-fos promoter may be an early target for signal transduction triggered by IFN alpha-receptor interaction.
Hannigan
G E
GE
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Williams
B R
BR
D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection / Q000235:genetics; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas