Antibody RING-Mediated Destruction of Endogenous Proteins
Abstract
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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BibTeX
@article{ibrahim2026antibody,
title = {{Antibody RING-Mediated Destruction of Endogenous Proteins}},
author = {Adel F.M. Ibrahim and Linnan Shen and Michael Tatham and David Dickerson and Alan Prescott and Naima Abidi and Dimitris Xirodimas and Ronald Hay},
journal = {Molecular Cell},
year = {2026},
month = sep,
doi = {10.1016/j.molcel.2020.04.032},
url = {https://hal.science/hal-05751779v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Antibody RING-Mediated Destruction of Endogenous Proteins
AU - Adel F.M. Ibrahim
AU - Linnan Shen
AU - Michael Tatham
AU - David Dickerson
AU - Alan Prescott
AU - Naima Abidi
AU - Dimitris Xirodimas
AU - Ronald Hay
PY - 2026
DA - 2026/09/16
JO - Molecular Cell
DO - 10.1016/j.molcel.2020.04.032
UR - https://hal.science/hal-05751779v1
AB - 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.
SN - 1097-2765
SN - 1097-4164
ER -