Apontic regulates cell proliferation and development by activating the expression ofhedgehogandcyclin E

Abstract

Hedgehog (Hh) signaling pathway and Cyclin E are key players in cell proliferation and development. Hyperactivation of hhand cyclin Ehas been linked to several types of cancer. However, transcriptional regulation of hhand cyclin Eare not well understood. Here we show that an evolutionarily conserved transcription factor Apontic (Apt) is an activator of hhand cyclin Ein Drosophila. Apt directly promotes the expression of hhand cyclin Ethrough its binding site in the promoter regions of hhand cyclin Eduring wing development. This Apt-dependent proper expression of hhand cyclin Eis required for cell proliferation and development of the wing. Apt-mediated expression of hhand cyclin Ecan direct proliferation of Hh-expressing cells and simultaneous growth, patterning and differentiation of Hh-recipient cells. The discovery of the coordinated expression of Hh and principal cell-cycle regulator Cyclin E by Apt implicates insight into the mechanism by which deregulated hhand cyclin Epromotes tumor formation.