Upload
steffi
View
64
Download
0
Tags:
Embed Size (px)
DESCRIPTION
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. - PowerPoint PPT Presentation
Citation preview
Smoothened and The Hedgehog (Hh) Pathway
James (Jay) LomaxBIOL 4453/19/13
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.
But what about the other players?
Tumor formation
Biological Role of the Hh Pathway
Drosophila
Biological Role of the Hh Pathway
Mice
Basal Cell Carcinoma
An open sore A reddish patch A shiny bump or nodule
A pink growth A scar-like area
Current Treatments
Hh/Smoothened Pathway Inhibitors
In theory: In reality:
Erivedge (Vismodegib)Cyclopamine
Veratrum californicum
References1. A positive role for Patched-Smoothened signaling in promoting cell proliferation during
normal head development in Drosophila. Baragur V. Shyamala and Krishna Moorthi Bhat2. GLI transcription factors: Mediators of oncogenic Hedgehog signalling. Maria Kasper,
Gerhard Regl, Anna-Maria Frischauf, Fritz Aberger3. 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 Beachy4. http://www.hedgehogpathway.com5. http://www.skincancer.org6. 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.
7. 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.