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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.

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Figure 1: Basic structure of the mammalian Hedgehog signalling pathway.
Figure 2: Hedgehog signal transduction at the primary cilium.
Figure 3: A speculative model for Smo regulation by Ptc and oxysterols.

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Acknowledgements

We apologize to colleagues whose primary references could not be cited due to space constraints and thank L. Milenkovic for comments and Fig. 2. R.R is the Robert Black Fellow of the Damon Runyon Cancer Research Fund and M.P.S is an investigator of the Howard Hughes Medical Institute.

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Rohatgi, R., Scott, M. Patching the gaps in Hedgehog signalling. Nat Cell Biol 9, 1005–1009 (2007). https://doi.org/10.1038/ncb435

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