Biochemical Mechanisms of Hedgehog Signal Transduction Through Primary Cilia in Medulloblastoma

Abstract

The Hedgehog pathway is essential for development, but misactivation of the Hedgehog pathway can cause cancer1 . Medulloblastomas are rare pediatric brain tumors with an incidence of 0.2-0.6 cases per 100,000 population2 , and approximately one-third of medulloblastomas are caused by Hedgehog pathway misactivation. Hedgehog signals are transduced through primary cilia on the surface of most cells3. When the Hedgehog pathway is off, Patched1 (PTCH1)localizes to cilia and inhibits Smoothened (SMO). Upon pathway activation, Hedgehog ligands such as Sonic Hedgehog (SHH) bind to PTCH1, removingPTCH1 from cilia, and allowing SMO to accumulate in cilia to activate the GLI family of transcription factors. How PTCH1 leaves cilia, how SMO accumulates to cilia, and how PTCH1 inhibits SMO to regulate oncogenic Hedgehog signaling is unknown.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2022
Accession Number
AD1207967

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  • David Raleigh

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  • University of California, San Francisco

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  • Abstracts
  • Biomedical Research
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