Figure 1.

The canonical HH signaling pathway. In the absence of the HH ligand (left), PTCH binds SMO, leading to its degradation. Microtubule complex containing Gli and SUFU is phosphorylated by GSK3β/PKA/CK1 to activate Gli proteins, which subsequently combine with β-TrCP to switch into transcriptional repressor (GLI-R). In the presence of HH ligand (right), SMO restriction by PTCH is relieved, active SMO moves to the primary cilium. Active Smo interacts with the SUFU/GLI complex, localized at the top of the primary cilium, GLI proteins from the complex switch into transcription activators (GLI-A), which then translocate to the nucleus and activate the HH target genes, including PTCH, GLI1, FOXA2, BCL-2, BCL-Xl, MYC, and CYCLIN family among others.