Figure 4. Model of GLI activation in BCC development.

Figure 4

Model of GLI activation in BCC development. Mutations resulting in loss of PTCH or gain of SMOH function (SMOH-A*) convert a latent inactive transcription factor - possibly GLI2 or GLI3 - into a strong activator form. Activated GLI2/3 directly induces transcription of GLI1 and possibly GLI2, although the GLI2 promoter has not yet been analyzed for the presence of functional GLI-binding sites. In wild-type cells, Notch-signaling negatively controls expression of GLI2. High-level expression of GLI1 and GLI2 in BCC is maintained by a positive feedback mechanism involving GLI1 and GLI2. In this scenario, GLI2 stimulates GLI1 expression by direct binding to the GLI1 promoter, while GLI1 in turn induces its own expression as well as GLI2 transcription probably via activation of an intermediate transcription factor. As a result, constitutive expression of GLI1 and GLI2 contributes to tumor formation by repressing differentiation signals and activating cell cycle progression genes, anti-apoptotic factors and genes promoting EMT and invasive growth. EMT: Epithelial-Mesenchymal Transition;

From: GLI Genes and Their Targets in Epidermal Development and Disease

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