The transactivation potential of a c-Myc N-terminal region (residues 92-143) is regulated by growth factor/Ras signaling.
The colony stimulating factor-1 receptor (CSF-1R) affects mitogenic growth and gene expression in NIH 3T3 cells through signaling pathways that require the products of the c-ras and c-myc proto-oncogenes. In this work we tested the hypothesis that there is direct communication between the Ras and Myc pathways. In transient transfection assays Ras increased by 5-fold transcriptional transactivation by chimeric c-Myc-Gal4 proteins. A constitutive active form of the CSF-1R also stimulated this activity and co-expression of a dominant negative ras gene ablated receptor stimulation. Deletion analysis of the c-Myc N-terminal region demonstrated that amino acid residues between positions 92 and 143 are the targets for Ras action. Transactivation by chimeric Myc proteins that were stably expressed could be transiently enhanced by either CSF-1 or serum, with peak activity occurring 2 h after mitogen stimulation. The steady-state levels of the chimeric c-Myc transactivators were increased following stimulation with CSF-1 or serum, but this increase in steady-state protein level did not strictly correlate with the increase in transactivation activity. Thus, Ras signaling may directly affect the activity of the c-Myc N-terminal region.
Colman
M S
MS
Department of Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
Ostrowski
M C
MC
D016475:3T3 Cells; D000818:Animals; D001769:Blood; D004268:DNA-Binding Proteins; D004988:Ethers, Cyclic / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics; D015870:Gene Expression; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D016296:Mutagenesis; D019319:Okadaic Acid; D010446:Peptide Fragments / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D014157:Transcription Factors; D015533:Transcriptional Activation; D014162:Transfection; D018631:ras Proteins / Q000378:metabolism* / Q000494:pharmacology
D004268:DNA-Binding Proteins; D004988:Ethers, Cyclic; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D010446:Peptide Fragments; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D019319:Okadaic Acid; D016173:Macrophage Colony-Stimulating Factor; D018631:ras Proteins