Dual control of myc expression through a single DNA binding site targeted by ets family proteins and E2F-1.
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.
Roussel
M F
MF
Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
Davis
J N
JN
Cleveland
J L
JL
Ghysdael
J
J
Hiebert
S W
SW
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D004247:DNA / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D004586:Electrophoresis; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics* / Q000502:physiology; D016259:Genes, myc / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics*; D056465:Retinoblastoma-Binding Protein 1; D016196:S Phase; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; C494041:ETS1 protein, human; C494042:Ets1 protein, mouse; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016271:Proto-Oncogene Proteins c-myc; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D004247:DNA