NF-kappa B-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts.
Interleukin 1 (IL-1) is a pluripotent cytokine involved in mediating a variety of physiological processes, including induction of cell proliferation upon wound healing. Treatment of quiescent FS-4 human dermal fibroblast cells with IL-1 activates c-myc gene transcription, and nuclear localization of NF-kappa B. Previously, we have noted that the murine c-myc gene contains two functional NF-kappa B sites located at -1101 to -1081 bp (upstream regulatory element [URE]) and +440 to +459 bp (internal regulatory element [IRE]) relative to the P1 promoter. Here we have demonstrated that IL-1 treatment induced binding of NF-kappa B-like proteins (p50/p65) to these c-myc elements. Heterologous promoter-CAT constructs driven by multiple copies of either the URE or IRE were IL-1 inducible when transfected into FS-4 cells. In contrast, constructs harboring elements with two G to C residue conversions, such that they were no longer able to bind NF-kappa B, were not responsive to IL-1. Mutation of these two base pairs at both NF-kappa B sites within a c-myc promoter/exon I-CAT construct, resulted in loss of inducibility with IL-1 upon transfection into quiescent FS-4 cells. Thus, IL-1 significantly induces c-myc expression through positive regulation by NF-kappa B, suggesting a role for this family of factors in activation of proliferation associated with wound healing.
Kessler
D J
DJ
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Duyao
M P
MP
Spicer
D B
DB
Sonenshein
G E
GE
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000528:radiation effects; D005347:Fibroblasts; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D016259:Genes, myc; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism / Q000528:radiation effects; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D007375:Interleukin-1; D016328:NF-kappa B; D009687:Nuclear Proteins; C070635:interleukin binding factor; D004247:DNA