THE DEUBIQUITINATION ENZYME FAT FACETS NEGATIVELY REGULATES RTK RAS/MAPK SIGNALING DURING DROSOPHILA EYE DEVELOPMENT/

The Drosophila fat facets (faf) gene encodes a deubiquitination enzyme with a putative function in proteasomal protein degradation. Mutants lacking zygotic Saf function develop to adulthood, but have rough eyes caused by the presence of one to two ectopic outer photoreceptors per ommatidium. Here we show that faf interacts genetically with the rece ptor tyrosine kinase (RTK)/Ras pathway, which induces photoreceptor di fferentiation in the developing eye. The results indicate that RTK/Ras signalling is increased in faf mutants, causing normally non-neuronal cells to adopt photoreceptor fate. Consistently, the protein level of at least one component of the Ras signal transduction pathway, the tr anscription factor D-Jun, is elevated in faf eye discs at the time whe n the ectopic photoreceptors are induced. We propose that defective ub iquitin-dependent proteolysis leads to increased and prolonged D-Jun e xpression, which together with other factors contributes to the induct ion of ectopic photoreceptors in faf mutants. These studies demonstrat e the relevance of ubiquitin-dependent protein degradation in the regu lation of RTK/Ras signal transduction in an intact organism. (C) 1997 Elsevier Science Ireland Ltd.