Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF.
A key event in the response of cells to proliferative signals is the rapid, transient induction of the c-fos proto-oncogene, which is mediated through the serum response element (SRE) in the fos promoter. Genomic footprinting and transfection experiments suggest that this activation occurs through a ternary complex that includes the serum response factor (SRF) and the ternary complex factor p62. Interaction of p62TCF with the SRF-SRE binary complex requires a CAGGA tract immediately upstream of the SRE. Proteins of the ets proto-oncogene family bind to similar sequences and we have found that a member of this family, Elk-1, forms SRF-dependent ternary complexes with the SRE. Elk-1 and p62TCF have the same DNA sequence requirements and antibodies against Elk-1 block the binding of both proteins. Furthermore, we show that like p62TCF, Elk-1 forms complexes with the yeast SRF-homologue MCM1 but not with yeast ARG80. But ARG80 mutants that convey interaction with p62TCF can also form complexes with Elk-1. The similarity, or even identity, between Elk-1 and p62TCF suggests a novel regulatory role for Ets proteins that is effected through interaction with other proteins, such as SRF. Furthermore, the possible involvement of an Ets protein in the control of c-fos has interesting implications for proto-oncogene cooperation in cellular growth control.
Hipskind
R A
RA
Hannover Medical School, Institute for Molecular Biology, Germany.
Rao
V N
VN
Mueller
C G
CG
Reddy
E S
ES
Nordheim
A
A
D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins; D000939:Epitopes / Q000032:analysis; D004926:Escherichia coli / Q000235:genetics; D016762:Genes, fos; D007106:Immune Sera; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000276:immunology; D050783:Proto-Oncogene Proteins c-ets; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D011519:Proto-Oncogenes; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics* / Q000276:immunology; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D050807:ets-Domain Protein Elk-1
D000906:Antibodies; D004268:DNA-Binding Proteins; D000939:Epitopes; D007106:Immune Sera; D046911:Macromolecular Substances; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D016760:Proto-Oncogene Proteins c-fos; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004247:DNA