Figure 1.

Inactive Hedgehog signalling. In the absence of Hh ligands, PTCH blocks the ciliary localization of SMO. The GLI transcription factors, located at the base of the primary cilium, are inhibited by the SUFU repressor complex. Then, KIF7 mediates GLI phosphorylation via PKA, CK1, and GSK3B kinases. Phosphorylated GLI1 is then ubiquitinated and totally degraded by the proteasome. However, GLI2 and GLI3 can be entirely or partially degraded. Incomplete degradation of GLI2/3 gives rise to the GLI repressor forms (GLI-R), which are translocated to the nucleus and inhibit the transcription of target genes. Image created with BioRender (BioRender.com).