Publications by authors named "Laura Aravena"
Hedgehog signaling governs critical processes in embryogenesis, adult stem cell maintenance, and tumorigenesis. The activating ligand, Sonic hedgehog (SHH), is highly hydrophobic because of dual palmitate and cholesterol modification, and thus, its release from cells requires the secreted SCUBE proteins. We demonstrate that the soluble SCUBE-SHH complex, although highly potent in cellular assays, cannot directly signal through the SHH receptor, Patched1 (PTCH1).
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- Smoothened is a key protein in Hedgehog signaling, crucial for development and cancer, and is activated by cholesterol binding to its cysteine-rich domain.
- The interaction causes significant changes in the protein's structure, revealing a unique inhibitory mechanism that, when disrupted, leads to its activation and oncogenic mutations.
- The study provides insights into how Smoothened activation affects cholesterol movement and describes how different antagonists, including cyclopamine, interfere with its function.