Figure 1. Hedgehog signaling pathway.

HH ligands (SHH, DHH or IHH) bind to the PTCH receptors (PTCH1 and PTCH2) and relieve the inhibition of SMO. HHIP, a negative inhibitor of HH signaling, can compete with PTCH receptors to bind HH ligand, resulting in the attenuation of HH signaling. SMO then transduces signals through the cytoplasmic SUFU-GLI complex, resulting in the activation and nuclear translocation of the downstream GLI transcription factors (GLI1-3). STK36 further promotes activation and nuclear accumulation of GLI by antagonizing SUFU. KIF7 regulates GLI-mediated transcription both positively and negatively through physical interaction with GLI and regulating the stability and degradation of GLI proteins.