Fig. 2

Canonical, ligand-dependent HH/GLI signaling. a In the absence of ligand, PTCH represses the ciliary translocation and activation of SMO, allowing the phosphorylation and proteolyic processing of full-length and SUFU-bound GLI protein into its C-terminally truncated repressor (GLI^R) within the primary cilium. In the nucleus, GLI^R binds to promoters of direct HH-target genes to prevent their transcription. b Binding of processed and post-translationally modified HH protein to its receptor PTCH abolishes the inhibitory effect of PTCH on SMO, allowing ciliary transport and activation of SMO. Active SMO prevents GLI^R processing and induces release of active GLI from its repressor SUFU. GLI activator (GLI^A) translocates to the nucleus, where it induces HH target gene expression