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Smoothened

Smoothened. Wear Sunscreen – stay smooth. Smoothened looks like a GPCR. Hedgehog pathway -- Drosophila. Adapted from Perrimon N, et al. Adapted from Tabata T, et al. Hedgehog binds Patched to relieve Patched inhibition of Smo. Ingham PW, et al. Phosphorylation. Shao Y, et al.

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Smoothened

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  1. Smoothened Wear Sunscreen – stay smooth

  2. Smoothened looks like a GPCR

  3. Hedgehog pathway -- Drosophila Adapted from Perrimon N, et al. Adapted from Tabata T, et al.

  4. Hedgehog binds Patched to relievePatched inhibition of Smo Ingham PW, et al.

  5. Phosphorylation Shao Y, et al.

  6. Regulated by graded hedgehog signal

  7. Hedgehog Signal Transduction in Mammals Tabata, T.

  8. Knockout Mouse Zhang XM, et al.

  9. Smo – stem cell maintenance • Regulates epidermal stem cell population Smo Ptc1 Zhou J, et al.

  10. Basal Cell Carcinoma Theskincancerfoundation.org

  11. Activated smoothened in Basal Cell Carcinoma • G-T transversion at 1604 bp –leucine > tryptophan • G-A transition at 1685 bp – encodes glutamine > arginine Xie J, et al.

  12. Mutant SMO Transgenic Mice Grachtchouk V, et al.

  13. SMOH mut – like human BCCs? Grachtchouk V, et al.

  14. SMOH as a therapeutic target Cyclopamine Veratrum californicum Bale AE

  15. Cyclopamine hates Smo Adapted from Chen JK, et al.

  16. SMOH as a therapeutic target Adapted from Arthar M, et al.

  17. Treatment of Human BCCs Adapted from Sinan TS, et al.

  18. Future Directions • Investigate smoothened – role in other cancers • Target smoothened for therapy

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