Our recent studies on human ets-1 proto-oncogene suggests alternative splicing and alternative usage of promoters. We plan to identify these promoters and their tissue specificity. We intend to study to mechanism of activation of human c-ets-1 proto-oncogene by making hybrid E-26 and c-ets-1 constructs to analyze the relevance of mutations in the oncogenic spectrum of E26 virus. We propose to study the cooperativity of ets oncogene with other oncogenes in the transformation process. Our recent results suggest ets-1 and the other members of ets oncogene (ets-2, erg- 1, erg-2, and elk-1) are all DNA binding proteins. We plan to map the sequence specific DNA binding domain of ets-1 (or v-ets) with the corresponding DNA binding domains of other members of ets oncogene superfamily and study the sequence specificity and the oncogenic potential of these hybrid constructs both in vivo and in vitro. We also intend to study protein-protein interaction of human c-ets-1 protein with the other nuclear oncoproteins and its effect on the biochemical properties of human c-ets-1 proto-oncogene.