ETS DOMAIN PROTEIN, LIN1

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The highly conserved Ras signaling pathway plays a major role in the determination of cell fates during development, and mutations in the ras proto-oncogene are commonly found in human cancers. ETS-domain proteins appear to be conserved mediators of Ras signaling, and the determination of how ETS transcription factors are regulated by Ras signaling and their function as effectors in various developmental processes is an important goal. I propose to combine genetic analyses of Ras-mediated signaling during C. elegans vulval development with biochemical investigations to elucidate the function of the ETS domain protein, LIN-1. The DNA binding activity and transactivation potential of LIN-1 will be ascertained, and target genes regulated by LIN-1 will be identified by biochemical methods. The role of ERK MAP kinase docking sites in the regulation of ETS-domain transcription factors in vivo will be ascertained, and peptides containing such docking sites will be developed as potential inhibitors of Ras-mediated events such as oncogenesis. Mutations in the network of genes surrounding lin-1 will be identified and characterized through the use of a genetic screen. These investigations will provide important clues about the conserved role of ETS-domain proteins as effectors of cell proliferation and fate determination.