Transgenic analyses of TGIF family proteins in Drosophila imply their role in cell growth.

TG-interacting factors (TGIFs) belong to a family of TALE-homeodomain proteins including TGIF, TGIF2, and TGIF2LX/Y (TGIF2 like on X or Y chromosome) in human. They potentially play important functions in various tissues during development. Mutations in TGIF are frequently associated with malformation of forebrain and facial structures; TGIF2 proteins are over-expressed in many ovarian cancer cell lines; and TGIF2LX/Y are specifically expressed in adult testis. The molecular functions of these proteins have been investigated mostly in cultured cells. TGIF and TGIF2 have been found as transcriptional repressors that modulate TGF-beta signaling. However, these findings are far from sufficient to explain their mutant phenotypes or expression patterns, and the functions of TGIF2LX/Y have never been reported. Here we use Drosophila as a model system to explore the functions of TGIF family proteins in vivo. We observed in fly tissues such as fat body, epithelia, and neuronal cells, that expressing human TGIF2 or human TGIF2LX generally inhibited cell growth in size and number. Co-expressing Drosophila Myc, Cyclin E, or human c-MycS partially rescued the growth inhibition induced by human TGIFs, whereas activated insulin pathway signaling did not. Taken together, we provide in vivo evidence for the potential functions of human TGIF2 and TGIF2LX in growth control. Additionally, we confirmed that Drosophila TGIFs are transcriptional activators by assaying their activities in spermatogenesis.