FIGURE 2.

A schematic description of Hedgehog signaling transduction. When HH is absent, the 12-span-membrane receptor protein PTCH1 (Patched1) inhibits SMO (Smoothened) accumulation in the primary cilium and consequently SMO activity. SuFu can form complexes with GLI proteins and inhibit them from entering the nucleus and their transcriptional activity. Several kinases, including PKA, GSK3β and CK1 phosphorylate the C-terminal of GLIs, leading to the truncated form of full length GLI. C-terminal deleted-GLIs are thought to be strong transcriptional repressors (GLI-R) that go into the nucleus and inhibit the transcription of target genes. Upon HH ligand binding, the inhibition from PTCH1 is released and SMO is activated and translocates into the primary cilium. Within the primary cilium, SMO forms a complex with EVC and EVC2 to transduce the HH signaling response. Activated SMO leads to the release of GLIs from the SuFu complex and GLIs go into the nucleus as transcriptional activators (GLI-A) that activate the transcription of target genes. Movement of GLI proteins within the primary cilium occurs in conjunction with KIF7, a member of the kinesin family of anterograde motor proteins. Abbreviations: HH, Hedgehog; DISP, Dispatched; PTCH1, Patched1; CDO, Cell adhesion molecule-related/down-regulated by oncogenes; BOC, brother of Cdo/biregional Cdon-binding protein; Gas1, Growth arrest specific 1; HHIP, Hedgehog-interacting protein; SMO, Smoothened; EVC, Ellis van Creveld syndrome protein; EVC2, Ellis van Creveld syndrome protein 2; GLI, Glioma-associated oncogene; SuFu, Suppressor of Fused; KIF7, Kinesin family member 7.