From Normal Development to Disease: The Biochemistry and Regulation of GLI2

GLI2 is an oncogene encoding a unique transcription factor with both repressor and activator functions. Vitally important in development, it is also thought to be necessary for homeostasis of adult cells. However, deregulation of the GLI2 protein can result in detrimental effects to an organism, such as congenital defects or cancer. Historically deemed an activator and effector molecule of the Hedgehog signaling pathway, GLI2 has since been shown to be a critical effector of other signaling pathways, thus positioning itself as a potent mediator of signaling crosstalk. While GLI2 activity can be modulated by a variety of signaling influences, its regulation at the gene level is less understood. Indeed, gene mutations in GLI2 have been reported, but these generally led to developmental defects and are less commonly identified in tumors as being a cause of its deregulation. While the biological importance of GLI2 overexpression in a multitude of unrelated cancers has been well established, questions about the mechanisms leading to aberrant expression have remained largely unanswered. Furthering our understanding of both the transcriptional regulation of the GLI2 gene and the target genes regulated by GLI2 may identify novel therapeutic targets for cancer treatment.