1. Smoothened and The Hedgehog (Hh) Pathway
James (Jay) Lomax
BIOL 445
3/19/13

2. What is Smoothened? (a protein conserved in Drosophila and Humans)
What it is
How its activated
Whats its function—receptor?
Conservation correlates with its important biological function

3. Biochemical Role of Hedgehog Pathway within the Cell
Stone et al.
Utilized a technique known as: co-immunoprecipitation

4. Key components of the Hh signaling pathway

5. Hedgehog Signaling Pathway

6. What happens when part of the pathway is mutated?
Xie et al.
Tumor formation
But what about the other players?

7. Biological Role of the Hh Pathway
Drosophila

8. Biological Role of the Hh Pathway
Mice

9. Basal Cell Carcinoma An open sore A reddish patch
A shiny bump or nodule
How basal cell and Hh are related?
A pink growth
A scar-like area

10. Current Treatments
Right--electrodessication

11. Hh/Smoothened Pathway Inhibitors
In theory:
In reality:
Veratrum californicum
Cyclopamine
Erivedge (Vismodegib)

12. References
A positive role for Patched-Smoothened signaling in promoting cell proliferation during normal head development in Drosophila. Baragur V. Shyamala and Krishna Moorthi Bhat
GLI transcription factors: Mediators of oncogenic Hedgehog signalling. Maria Kasper, Gerhard Regl, Anna-Maria Frischauf, Fritz Aberger
Hedgehog-Regulated Processing of Gli3 Produces an Anterior/Posterior Repressor Gradient in the Developing Vertebrate Limb. Cell, Volume 100, Issue 4, 18 February 2000, Pages 423–434. Baolin Wang , John F Fallon , Philip A Beachy
Stone, D. M., Hynes, M., Armanini, M., Swanson, T. A., Gu, Q., Johnson, R. L., Scott, M. P., Pennica, D., Goddard, A., Phillips, H., Noll, M., Hooper, J. E., de Sauvage, F., Rosenthal, A. The tumour-suppressor gene Patched encodes a candidate receptor for Sonic hedgehog. Nature 384: , 1996.
Xie, J., Murone, M., Luoh, S.-M., Ryan, A., Gu, Q., Zhang, C., Bonifas, J. M., Lam, C.-W., Hynes, M., Goddard, A., Rosenthal, A., Epstein, E. H., Jr., de Sauvage, F. J. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature 391: 90-92, 1998.