NF-κB-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts

• Published in: The Journal of experimental medicine 1992-09, Vol.176 (3), p.787-792
• Main Authors: KESSLER, D. J, DUYAO, M. P, SPICER, D. B, SONENSHEIN, G. E
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Cell Line; Cloning, Molecular; DNA; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - radiation effects; Fibroblasts; Forkhead Transcription Factors; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Genes, myc; Humans; Interleukin-1 - physiology; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; NF-kappa B - physiology; Nuclear Proteins - metabolism; Nuclear Proteins - radiation effects; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Transcription, Genetic; Transcription. Transcription factor. Splicing. Rna processing; Transcriptional Activation; Ultraviolet Rays
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.176.3.787

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.