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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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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Naisbitt, S., Kim, E., Tu, J. C., Xiao, B., Sala, C., Valtschanoff, J., Weinberg, R. J., Worley, P. F., & Sheng, M. (1999) · Neuron · doi:10.1016/s0896-6273(00)80809-0 · Cited by 1,009 · see citing works
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TEL Is a Sequence-specific Transcriptional Repressor
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Mae mediates MAP kinase phosphorylation of Ets transcription factors in Drosophila
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Native interface of the SAM domain polymer of TEL
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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
- ORCID
- Venue
- The EMBO Journal
- Published
- 1997-01-01
- Volume
- 16
- Issue
- 1
- Pages
- 69-82
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1169615
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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