Figure 2.

The HH signalling pathway. HH ligands bind to the membrane-associated protein PTCH1 and inhibit its function. PTCH1 inhibits SMO by preventing it from translocating to the primary cilium. SMO inhibits SUFU which, in turn, inhibits the activation and translocation of GLI1 and GLI2 to the nucleus. SUFU also activates GLI3, which is processed by proteolytic cleavage to become a transcriptional repressor. GLI1 and GLI2 activate transcription of several target genes, including themselves and PTCH1. The loss of PTCH leads to constitutive activation of the pathway. Small molecule inhibitors bind and inhibit SMO.