Patching the gaps in Hedgehog signalling.
The Hedgehog (Hh) pathway plays central roles in animal development and stem-cell function. Defects in Hh signalling lead to birth defects and cancer in humans. The first and often genetically damaged step in this pathway is the interaction between two membrane proteins - Patched (Ptc), encoded by a tumour suppressor gene, and Smoothened (Smo), encoded by a proto-oncogene. Recent work linking Hh signalling to sterol metabolites and protein-trafficking events at the primary cilium promises to shed light on the biochemical basis of how Patched inhibits Smoothened, and to provide new avenues for cancer treatment.
Rohatgi
Rajat
R
Department of Developmental Biology, Howard Hughes Medical Institute, Clark Center West W252, 318 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305-5439, USA.
Scott
Matthew P
MP
D000818:Animals; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy; D000072079:Patched Receptors; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D000072086:Smoothened Receptor
D053823:Hedgehog Proteins; C000715470:MAS1 protein, human; D000072079:Patched Receptors; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor