A domain of TEL conserved in a subset of ETS proteins defines a specific oligomerization interface essential to the mitogenic properties of the TEL-PDGFR beta oncoprotein

EMBO J. 1997 Jan 2;16(1):69-82. doi: 10.1093/emboj/16.1.69.


TEL is a novel member of the ETS family of transcriptional regulators which is frequently involved in human leukemias as the result of specific chromosomal translocations. We show here by co-immunoprecipitation and GST chromatography analyses that TEL and TEL-derived fusion proteins form homotypic oligomers in vitro and in vivo. Deletion mutagenesis identifies the TEL oligomerization domain as a 65 amino acid region which is conserved in a subset of the ETS proteins including ETS-1, ETS-2, FLI-1, ERG-2 and GABP alpha in vertebrates and PNTP2, YAN and ELG in Drosophila. TEL-induced oligomerization is shown to be essential for the constitutive activation of the protein kinase activity and mitogenic properties of TEL-platelet derived growth factor receptor beta (PDGFR beta), a fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic leukemia harboring a t(5;12) chromosomal translocation. Swapping experiments in which the TEL oligomerization domain was exchanged by the homologous domains of representative vertebrate ETS proteins including ETS-1, ERG-2 and GABP alpha show that oligomerization is a specific property of the TEL amino-terminal conserved domain. These results indicate that the amino-terminal domain conserved in a subset of the ETS proteins has evolved to generate a specialized protein-protein interaction interface which is likely to be an important determinant of their specificity as transcriptional regulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Division
  • Conserved Sequence
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / physiology*
  • Drosophila
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Oncogene Proteins / chemistry
  • Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-ets
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor / chemistry
  • Receptors, Platelet-Derived Growth Factor / physiology*
  • Repressor Proteins*
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • ETS translocation variant 6 protein
  • Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • Transcription Factors
  • Receptor, Platelet-Derived Growth Factor beta
  • Receptors, Platelet-Derived Growth Factor

Associated data

  • GENBANK/L19541