Two independent activation domains in c-Ets-1 and c-Ets-2 located in non-conserved sequences of the ets gene family

Oncogene. 1992 Feb;7(2):249-56.

Abstract

The c-Ets-1 oncoprotein is a transcription activator that specifically binds to DNA. We show, using fusion proteins with heterologous DNA-binding domains, that chicken c-Ets-1 (p68) contains two independent activation domains. The N-terminal activation domain is absent in c-Ets-1 (p54) that is generated from an alternatively spliced mRNA. A closely related member of the ets gene family, c-Ets-2, also contains two separate activation domains. They lie in the regions of the protein that are least conserved with c-Ets-1, suggesting that the activating function will determine the different physiological roles of these two proteins. The activation domains of c-Ets-1 (p68) and -2 are separated by a moderately conserved region that does not activate on its own. These sequences appear to affect stimulation by the domains, suggesting that they regulate transcription activation. Competition experiments show that c-Ets-1 and -2 interact with a common limiting coactivator. These studies provide important clues about the physiological roles of closely related members of the ets gene family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Cell Compartmentation
  • Cells, Cultured
  • DNA-Binding Proteins / chemistry*
  • In Vitro Techniques
  • Mice
  • Molecular Weight
  • Mutagenesis, Site-Directed
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism
  • Oligodeoxyribonucleotides / chemistry
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins / chemistry*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins*
  • Structure-Activity Relationship
  • Trans-Activators*
  • Transcription Factors / chemistry*

Substances

  • DNA-Binding Proteins
  • ERF protein, human
  • Ets2 protein, mouse
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Protein c-ets-2
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Trans-Activators
  • Transcription Factors