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Targeting of proteins to membranes through hedgehog auto-processing
Nature Biotechnologyvolume 21, pages936–940 (2003)Cite this article
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Abstract
Hedgehog proteins use an auto-processing strategy to generate cholesterol-conjugated peptide products that act as extracellular ligands in a number of developmental signaling pathways. We describe an approach that takes advantage of the hedgehog auto-processing reaction to carry out intracellular modification of heterologous proteins, resulting in their localization to cell membranes. Such processing occurs spontaneously, without accessory proteins or modification by other enzymes. Using the green fluorescent protein (GFP) and the product of theHras as model proteins, we demonstrate the use of hedgehog auto-processing to process heterologous N-terminal domains and direct the resulting biologically active products to cell membranes. This system represents a tool for targeting functional peptides and proteins to cell membranes, and may also offer a means of directing peptides or other small molecules to components of cholesterol metabolism or regulation.
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Acknowledgements
The authors wish to thank Peter Erhardt of the Boston Biomedical Research Institute for use of the confocal microscopy facility.
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GenPath Pharmaceuticals, 300 Technology Square, Cambridge, 02139, Massachusetts, USA
Sylvie Vincent
SelectX Pharmaceuticals, 44 Hartwell Avenue, Lexington, 02421, Massachusetts, USA
Abraham Thomas & Bradley Brasher
Novartis Institutes for Biomedical Research, 100 Technology Square, Cambridge, 02139, Massachusetts, USA
John D Benson
- Sylvie Vincent
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Correspondence toJohn D Benson.
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Vincent, S., Thomas, A., Brasher, B.et al. Targeting of proteins to membranes through hedgehog auto-processing.Nat Biotechnol21, 936–940 (2003). https://doi.org/10.1038/nbt844
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