Cited by 207Genomics and Chromatin DynamicsRetinoids in leukemia and cellular processesT-cell and Retrovirus Studies

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

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Jousset, Christine, Carron, Clémence, Boureux, Anthony, Quang, Christine Tran, Oury, Cécile, Dusanter‐Fourt, Isabelle, Charon, Martine, Levin, Jonathan +2 more·1997·The EMBO Journal

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.

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Crossref · 10.1093/emboj/16.1.69

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Authors
Jousset, C., Carron, C., Boureux, A., Quang, C. T., Oury, C., Dusanter‐Fourt, I., Charon, M., Levin, J., Bernard, O., & Ghysdael, J.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Inserm (FR)
  • Institut National de la Recherche Agronomique (FR)
Corresponding author
Jousset, Christine
Venue
The EMBO Journal
Published
1997-01-01
Volume
16
Issue
1
Pages
69-82
ISSN
  • 0261-4189 (ISSN-L)
  • 1460-2075
OpenAlex
W2018075615
Cited by
207
References
105
Citations by year
2026: 1 · 2025: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 7
FWCI
7.00
Type
journal article
Language
en
Open access
Locations
  • The EMBO Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • Open Repository and Bibliography (University of Liège) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
Keywords
TEL, ETS transcription factors, protein oligomerization, oligomerization domain, protein-protein interfaces, mitogenic activity, chronic myelomonocytic leukemia, ETS1, FLI1, ERG, leukemia, domain swapping
MeSH terms
ETS Translocation Variant 6 Protein, Amino Acid Sequence, Animals, Binding Sites, Cell Division, DNA-Binding Proteins, Drosophila, HeLa Cells, Humans, Molecular Sequence Data, Repressor Proteins, Transcription Factors, Oncogene Proteins, Conserved Sequence, Sequence Deletion, Sequence Homology, Amino Acid, Receptors, Platelet-Derived Growth Factor, Receptor, Platelet-Derived Growth Factor beta, Proto-Oncogene Proteins c-ets

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