Expanding the Iroquois genes repertoire: a non-transcriptional function in cell cycle progression

Drosophila Iroquois (Iro) proteins are components of the TALE homeodomain family of transcriptional regulators. They play key roles in territorial specification and pattern formation. A recent study has disclosed a novel developmental function of the Iro proteins. In the eye and wing imaginal discs, they can regulate the size of the territories that they specify. They do so by cell-autonomously controlling cell cycle progression. Indeed, Iro proteins down-regulate the activity of the CyclinE/Cdk2 complex by a transcription-independent mechanism. This novel function is executed mainly through 2 evolutionarily conserved domains of the Iro proteins: the Cyclin Binding Domain and the IRO-box, which mediate their binding to CyclinE-containing protein complexes. Here we discuss the functional implications of the control of the cell cycle by Iro proteins for development and oncogenesis.