Regulation of the Hedgehog pathway

Hedgehog signaling is regulated at various levels within the pathway. At the cell surface, several transmembrane proteins regulate Hedgehog binding to PTCH. The negative regulator Hhip protein competes with PTCH for Hedgehog ligand binding.^5,6 The positive regulators Cdo, Boc, and Gas1 enhance the binding of the Hedgehog ligands to PTCH.^7-9 Inside the cell, numerous components regulate the transport of Hedgehog pathway components into the cilium.¹⁰ Finally, Sufu is found downstream of SMO and is an important negative regulator of Gli transcription factor activity.^11,12