Back to Search
Start Over
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
- Source :
- EMBO Journal, EMBO Journal, EMBO Press, 1997, 16 (1), pp.69-82. ⟨10.1093/emboj/16.1.69⟩, EMBO Journal, 1997, 16 (1), pp.69-82. ⟨10.1093/emboj/16.1.69⟩
- Publication Year :
- 1997
- Publisher :
- HAL CCSD, 1997.
-
Abstract
- International audience; 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.
- Subjects :
- Oncogene Proteins
[SDV]Life Sciences [q-bio]
Molecular Sequence Data
Protein domain
Biology
DNA-binding protein
General Biochemistry, Genetics and Molecular Biology
Conserved sequence
Receptor, Platelet-Derived Growth Factor beta
03 medical and health sciences
0302 clinical medicine
hemic and lymphatic diseases
Animals
Humans
Receptors, Platelet-Derived Growth Factor
Amino Acid Sequence
Molecular Biology
Transcription factor
Peptide sequence
Conserved Sequence
Sequence Deletion
030304 developmental biology
0303 health sciences
Binding Sites
Proto-Oncogene Proteins c-ets
Sequence Homology, Amino Acid
General Immunology and Microbiology
General Neuroscience
BIOLOGIE MOLECULAIRE
Fusion protein
Molecular biology
CANCER
[SDV] Life Sciences [q-bio]
DNA-Binding Proteins
Repressor Proteins
030220 oncology & carcinogenesis
Drosophila
Cell Division
Research Article
HeLa Cells
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 02614189 and 14602075
- Database :
- OpenAIRE
- Journal :
- EMBO Journal, EMBO Journal, EMBO Press, 1997, 16 (1), pp.69-82. ⟨10.1093/emboj/16.1.69⟩, EMBO Journal, 1997, 16 (1), pp.69-82. ⟨10.1093/emboj/16.1.69⟩
- Accession number :
- edsair.doi.dedup.....110623d86796de9747a1faec4b2ed11e