A DOMAIN OF TEL CONSERVED IN A SUBSET OF ETS PROTEINS DEFINES A SPECIFIC OLIGOMERIZATION INTERFACE ESSENTIAL TO THE MITOGENIC PROPERTIES OFTHE TEL-PDGFR-BETA ONCOPROTEIN

TEL is a novel member of the ETS family of transcriptional regulators which is frequently involved in human leukemias as the result of speci fic chromosomal translocations. We show here by co-immunoprecipitation and GST chromatography analyses that TEL and TEL-derived fusion prote ins form homotypic oligomers in vitro and in vivo. Deletion mutagenesi s identifies the TEL oligomerization domain as a 65 amino acid region which is conserved in a subset of the ETS proteins including ETS-1, ET S-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 f or the constitutive activation of the protein kinase activity and mito genic 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 tr anslocation. Swapping experiments in which the TEL oligomerization dom ain was exchanged by the homologous domains of representative vertebra te ETS proteins including ETS-1, ERG-2 and GABP alpha show that oligom erization is a specific property of the TEL amino-terminal conserved d omain. 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 import ant determinant of their specificity as transcriptional regulators.