Article Dans Une Revue Molecular Cell Année : 2020

Antibody RING-Mediated Destruction of Endogenous Proteins

Résumé

To understand gene function, the encoding DNA or mRNA transcript can be manipulated and the consequences observed. However, these approaches do not have a direct effect on the protein product of the gene, which is either permanently abrogated or depleted at a rate defined by the half-life of the protein. We therefore developed a single-component system that could induce the rapid degradation of the specific endogenous protein itself. A construct combining the RING domain of ubiquitin E3 ligase RNF4 with a protein-specific camelid nanobody mediates target destruction by the ubiquitin proteasome system, a process we describe as antibody RING-mediated destruction (ARMeD). The technique is highly specific because we observed no off-target protein destruction. Furthermore, bacterially produced nanobody-RING fusion proteins electroporated into cells induce degradation of target within minutes. With increasing availability of protein-specific nanobodies, this method will allow rapid and specific degradation of a wide range of endogenous proteins.

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hal-03026194 , version 1 (28-10-2025)

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Adel F.M. Ibrahim, Linnan Shen, Michael Tatham, David Dickerson, Alan Prescott, et al.. Antibody RING-Mediated Destruction of Endogenous Proteins. Molecular Cell, 2020, 79 (1), pp.155-166.e9. ⟨10.1016/j.molcel.2020.04.032⟩. ⟨hal-03026194⟩
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