Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins
The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombin...
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| Hauptverfasser: | , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 January 2024
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| In: |
EMBO reports
Year: 2024, Jahrgang: 25, Heft: 3, Pages: 951-970 |
| ISSN: | 1469-3178 |
| DOI: | 10.1038/s44319-024-00063-3 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44319-024-00063-3 Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.1038/s44319-024-00063-3 
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| Verfasserangaben: | Janika Schmitt, Emma Poole, Ian Groves, David J Owen, Stephen C Graham, John Sinclair & Bernard T Kelly |
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| 520 | |a The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombinant antibodies genetically fused to this domain drive the degradation of membrane proteins that undergo constitutive internalisation and recycling, including the transferrin receptor and the human cytomegalovirus latency-associated protein US28. We term this approach PACTAC (PCSK9-Antibody Clearance-Targeting Chimeras). | ||
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| 700 | 1 | |a Sinclair, John |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kelly, Bernard T. |e VerfasserIn |4 aut | |
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