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Smoothened and The Hedgehog ( Hh ) Pathway

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.

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Smoothened and The Hedgehog ( Hh ) Pathway

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  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) 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. HedgehogSignaling 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 A reddish patch A shiny bump or nodule An open sore A scar-like area A pink growth

  10. Current Treatments

  11. Hh/Smoothened Pathway Inhibitors In theory: In reality: Veratrumcalifornicum 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 MoorthiBhat • 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.

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