This three-year award will support U.S.-France cooperative research in biochemical genetics among several American and French researchers at the University of Colorado and the Laboratory for Molecular Genetics, French National Center for Scientific Research, in Strasbourg, France. The investigators are Arthur Gutierrez-Hartmann, Andrew Bradford and Bohdan Wasylyk. The objectives of their research are to define regions of the molecules Ets-1 protoocogene and GHF-1/Pit-1 and their role in cellular differentiation and malignant transformation. They will perform site-directed mutagenesis experiments in order to define regions of the two proteins that are involved in mediating their interaction. The U.S. investigators bring to this collaboration their expertise in hormonal regulation of gene expression. This is complemented by the French investigator's expertise in the Ets molecules and takes advantage of French techniques in generating on site Ets mutants. The results will advance our understanding of molecular mechanisms common to all cell types, healthy and malignant, and cell-specific responses.