Tumor suppressor gene OSCP1/NOR1 regulates apoptosis, proliferation, differentiation, and ROS generation during eye development of Drosophila melanogaster.

Abstract

OSCP1/NOR1 (organic solute carrier partner 1/oxidored nitrodomain-containing protein 1) is a known tumor suppressor protein. OSCP1 has been reported to mediate transport of various organic solutes into cells; however, its role during development has not yet been addressed. Here we report the results of studies on dOSCP1 (the Drosophila ortholog of hOSCP1) to elucidate the role of OSCP1/NOR1 during development. Knockdown of dOSCP1 in the eye imaginal discs induced a rough-eye phenotype in adult flies. This phenotype resulted from induction of caspase-dependent apoptosis followed by a compensatory cell proliferation and generation of reactive oxygen species in eye imaginal discs. The induction of apoptosis appears to be associated with down-regulation of the anti-apoptotic Buffy gene and up-regulation of the pro-apoptotic Debcl gene. These effects of knockdown of dOSCP1 lead to mitochondrial fragmentation, degradation, and a shortfall in ATP production. We also found that knockdown of dOSCP1 causes a defect in cone cell and pigment cell differentiation in pupal retinae. Moreover, mutations in epidermal growth factor receptor pathway-related genes, such as Spitz and Drk, enhanced the rough-eye phenotype induced by dOSCP1 knockdown. These results suggest that dOSCP1 positively regulates the epidermal growth factor receptor signaling pathway. Overall, our findings indicate that dOSCP1 plays multiple roles during eye development in Drosophila.