Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF

Nature. 1991 Dec 19-26;354(6354):531-4. doi: 10.1038/354531a0.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies
  • Base Sequence
  • Binding Sites
  • DNA / genetics
  • DNA-Binding Proteins*
  • Epitopes / analysis
  • Escherichia coli / genetics
  • Genes, fos*
  • Immune Sera
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / immunology
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-fos / genetics*
  • Proto-Oncogenes*
  • Retroviridae Proteins, Oncogenic / genetics*
  • Retroviridae Proteins, Oncogenic / immunology
  • Saccharomyces cerevisiae / genetics
  • Sequence Homology, Nucleic Acid
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection
  • ets-Domain Protein Elk-1

Substances

  • Antibodies
  • DNA-Binding Proteins
  • Epitopes
  • Immune Sera
  • Macromolecular Substances
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-fos
  • Retroviridae Proteins, Oncogenic
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • DNA