Projects per year
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.
|Number of pages||12|
|Early online date||25 May 2020|
|Publication status||Published - 2 Jul 2020|
- E3 ligase
- nanobody-RING fusion
- protein degradation
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
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Establishing the Basis for Selectivity in the SUMO Spray (Investigator Award)
1/02/20 → 31/01/25
Harnessing the PML-SUMO-RNF4 Axis for Cancer Therapy (Programme Grant)
1/12/16 → 30/09/22