PHOTORECEPTOR CELL-DIFFERENTIATION REQUIRES REGULATED PROTEOLYSIS OF THE TRANSCRIPTIONAL REPRESSOR TRAMTRACK

The transcription repressor Tramtrack (TTK) is found in cone cells but not photoreceptor cells of the Drosophila eye. We show that down-regu lation of TTK expression occurs in photoreceptor cells and is required for their fate determination. Down-regulation requires the presence o f Phyllopod (PHYL), which is induced by the RAS pathway, and Seven In Absentia (SINA). Loss of either gene causes accumulation of TTK in pho toreceptor cells, and TTK does not accumulate in cone cells if both PH YL and SINA are present. We report that SINA and PHYL promote ubiquiti nation and rapid degradation of TTK by the proteasome pathway in cell culture, and both SINA and PHYL bind to the N-terminal domain of TTK. These results argue that photoreceptor differentiation is regulated by the RAS pathway through targeted proteolysis of the TTK repressor.