title: 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.
abstract: 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.
authors.affiliation: CNRS UMR 146, Institut Curie-Section de Recherche, Centre Universitaire, Orsay, France.
authors.forename: C
authors.initials: C
authors.lastname: Jousset
authors.forename: C
authors.initials: C
authors.lastname: Carron
authors.forename: A
authors.initials: A
authors.lastname: Boureux
authors.forename: C T
authors.initials: CT
authors.lastname: Quang
authors.forename: C
authors.initials: C
authors.lastname: Oury
authors.forename: I
authors.initials: I
authors.lastname: Dusanter-Fourt
authors.forename: M
authors.initials: M
authors.lastname: Charon
authors.forename: J
authors.initials: J
authors.lastname: Levin
authors.forename: O
authors.initials: O
authors.lastname: Bernard
authors.forename: J
authors.initials: J
authors.lastname: Ghysdael
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D004330:Drosophila; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000737:chemistry / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry / Q000502:physiology*; D012097:Repressor Proteins; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D004268:DNA-Binding Proteins; D015513:Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein