生物
泛素连接酶
内生
泛素
蛋白质降解
融合蛋白
蛋白酶体
泛素结合酶
细胞生物学
RNF4型
DDB1型
抗体
分子生物学
基因
遗传学
生物化学
锌指
转录因子
重组DNA
作者
Adel Ibrahim,Linnan Shen,Michael H. Tatham,David Dickerson,Alan R. Prescott,Naima Abidi,Dimitris P. Xirodimas,Ronald T. Hay
出处
期刊:Molecular Cell
[Elsevier]
日期:2020-07-01
卷期号:79 (1): 155-166.e9
被引量:38
标识
DOI:10.1016/j.molcel.2020.04.032
摘要
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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