Smoothened
description
Transcript of Smoothened
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SmoothenedWear Sunscreen – stay smooth
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Smoothened looks like a GPCR
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Hedgehog pathway -- Drosophila
Adapted from Tabata T, et al.
Adapted from Perrimon N, et al.
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Hedgehog binds Patched to relievePatched inhibition of Smo
Ingham PW, et al.
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Phosphorylation
Shao Y, et al.
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Regulated by graded hedgehog signal
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Hedgehog Signal Transduction in Mammals
Tabata, T.
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Knockout Mouse
Zhang XM, et al.
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• Regulates epidermal stem cell population
Smo – stem cell maintenance
Smo
Ptc1
Zhou J, et al.
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Basal Cell Carcinoma
Theskincancerfoundation.org
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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.
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Mutant SMO Transgenic Mice
Grachtchouk V, et al.
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SMOH mut – like human BCCs?
Grachtchouk V, et al.
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SMOH as a therapeutic targetCyclopamine
Bale AE
Veratrum californicum
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Cyclopamine hates Smo
Adapted from Chen JK, et al.
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SMOH as a therapeutic target
Adapted from Arthar M, et al.
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Treatment of Human BCCs
Adapted from Sinan TS, et al.
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Future Directions
• Investigate smoothened – role in other cancers
• Target smoothened for therapy