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

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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 GABPα 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 β (PDGFRβ), 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 GABPα 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.