Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1.

Roussel MF, Davis JN, Cleveland JL, Ghysdael J, Hiebert SW
Oncogene. 1994 9 (2): 405-15

PMID: 8290253

NIH3T3 cells expressing a mutant colony-stimulating factor-1 receptor (CSF-1R) containing a phenylalanine for tyrosine substitution in the tyrosine kinase domain at codon 809 exhibit defective myc regulation and do not enter S phase when stimulated by CSF-1. Enforced expression of either ets-1 or ets-2 in these cells restores their mitogenic response, albeit less efficiently than myc itself, suggesting that ets proteins may regulate c-myc expression. Ets-1 transactivates reporter genes driven by the human and mouse c-myc promoters through the binding site for the transcription factor E2F, the latter being required for E1A- and serum-induced c-myc expression. Analysis of E2F-1 sequences identified a minimal DNA binding domain that is related to those of ets proteins. Although E2F and ets proteins interact with similar consensus DNA binding sites, in vitro binding assays revealed that E2F can bind DNA as a homodimer, whereas ets proteins bind these sites as monomers. E2F and ets proteins do not form heterodimers in vitro and do not transactivate c-myc synergistically. Thus, E2F-1 and ets family members may independently regulate c-myc transcription through the same binding site at different times following growth factor stimulation.

MeSH Terms (29)

Amino Acid Sequence Animals Base Sequence Carrier Proteins Cell Cycle Proteins Cell Line DNA DNA-Binding Proteins E2F1 Transcription Factor E2F Transcription Factors Electrophoresis Fibroblasts Gene Expression Regulation Genes, myc Mice Molecular Sequence Data Promoter Regions, Genetic Protein Binding Proto-Oncogene Protein c-ets-1 Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets Proto-Oncogene Proteins c-myc Retinoblastoma-Binding Protein 1 S Phase Transcription, Genetic Transcriptional Activation Transcription Factor DP1 Transcription Factors Transfection

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