An ever-expanding family of ets-related genes has been found in the human genome, as well as in that of other species. Features of this ets family include a DNA-binding domain, as well as a helix-loop-helix motif, which has been postulated to be a site for protein-protein interaction. The goal of this project is to identify proteins which interact with individual ETS proteins, and thus give rise to functional differences among the members of the ets family. To this end, the yeast two-hybrid system has been used to identify ets-interacting proteins. ETS1, ETS2, and ERGB genes have been placed into shuttle vectors which express the Ets proteins fused with the yeast GAL4 DNA binding domain. These Ets fusion constructs are co-transformed along with a cDNA library which is expressed as a fusion protein with the GAL4 activation domain. Growth of colonies in selective media will indicate an interaction between Ets and library proteins. Following confirmation of these protein-protein interactions, the domains of Ets and interacting protein(s) which are required for the interaction will be defined.