Smoothened and The Hedgehog
(Hh) Pathway
James (Jay) Lomax
BIOL 445
3/19/13
What is Smoothened?
(a protein conserved in Drosophila and Humans)
Conservation correlates with its important biological function
Biochemical Role of Hedgehog
Pathway within the Cell
Stone et al.
Utilized a technique known as: co-immunoprecipitation
Key components of the Hh signaling
pathway
Hedgehog Signaling Pathway
What happens when part of the
pathway is mutated?
Xie et al.
Tumor formation
But what about the other players?
Biological Role of the Hh Pathway
Drosophila
Biological Role of the Hh Pathway
Mice
Basal Cell Carcinoma
A reddish patch
An open sore
A pink growth
A shiny bump or nodule
A scar-like area
Current Treatments
Hh/Smoothened Pathway Inhibitors
In theory:
In reality:
Veratrum
californicum
Cyclopamine
Erivedge (Vismodegib)
References
1.
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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
http://www.hedgehogpathway.com
http://www.skincancer.org
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: 129-134, 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.