Characterization of dSki and its relationship to Decapentaplegic signalling in Drosophila

Vertebrate members of the ski/snoN family of proto-oncogenes antagonize TGFβ and BMP signalling in a variety of experimental situations. This activity of Ski/SnoN proteins is related to their ability to interact with Smads, the proteins acting as key mediators of the transcriptional response to the TGFβ superfamily members. However, despite extensive efforts to identify the physiological roles of the Ski/SnoN proteins, it is not yet clear whether they participate in regulating Activin and/or BMP signalling during normal development. It is therefore crucial to examine their roles in vivo, mostly because of the large number of known Ski/SnoN-interacting proteins and the association between the up-regulation of these genes and cancer progression. Here we characterise the Drosophila homolog to vertebrate ski and snoN genes. The Drosophila dSki protein retains the ability of its vertebrate counterparts to antagonize BMP signalling, it is localized to both the nucleus and the cytoplasm and it does not interfere with Mad phosphorylation. The elimination of dski reduces viability and causes female sterility, but the surviving homozygous flies have wings of normal size and pattern. We suggest that the presence of other TGFβ antagonists might make redundant the negative effects of dSki on signalling mediated by these pathways. The Ski/SnoN repression of the pathway might constitute a “security system” for the organism in cases where the TGFβ signal is unbalanced.