Groucho mediates a subset of Capicua repressor activities in Drosophila. Leiore Ajuria¹, Claudia Nieva¹, Marta Forés¹, Rona Grossman², Sergio González-Crespo¹, Ze'ev Paroush², Gerardo Jiménez^1,3. 1) IBMB-CSIC, Parc Científic de Barcelona, Barcelona, Spain; 2) Dept. of Developmental Biology and Cancer Research, IMRIC, The Hebrew Univ., Jerusalem, Israel; 3) ICREA, Barcelona, Spain.

   The HMG-box protein Capicua (Cic) is a general sensor of RTK-Ras-MAPK signaling pathways. In different patterning systems, Cic represses genes regulated by RTK signaling; following RTK activation, Cic repression is relieved and this allows the expression of responsive genes. We are investigating the mechanisms by which Drosophila Cic represses transcription, and their potential conservation in mammals, where Cic has been implicated in cancer and neurodegeneration. Using a combination of genetic and molecular assays, we find that Cic repression in the blastoderm embryo is strictly dependent on the Groucho (Gro) corepressor. This Cic-Gro interaction may not involve a direct physical association, since we do not observe co-immunoprecipitation of both proteins under conditions where Gro binds efficiently to other repressors. In contrast, Cic repressor activity does not require Gro in tissues such as the wing or the ovarian follicular epithelium. In all cases, the highly conserved C1 motif of Cic is essential for repression. Thus, Cic displays both common and context-specific requirements to perform its multiple repressor functions in development.