A Method for the Acute and Rapid Degradation of Endogenous Proteins

Dean Clift, William A McEwan, Larisa I Labzin, Vera Konieczny, Binyam Mogessie, Leo C James, Melina Schuh

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

Methods for the targeted disruption of protein function have revolutionized science and greatly expedited the systematic characterization of genes. Two main approaches are currently used to disrupt protein function: DNA knockout and RNA interference, which act at the genome and mRNA level, respectively. A method that directly alters endogenous protein levels is currently not available. Here, we present Trim-Away, a technique to degrade endogenous proteins acutely in mammalian cells without prior modification of the genome or mRNA. Trim-Away harnesses the cellular protein degradation machinery to remove unmodified native proteins within minutes of application. This rapidity minimizes the risk that phenotypes are compensated and that secondary, non-specific defects accumulate over time. Because Trim-Away utilizes antibodies, it can be applied to a wide range of target proteins using off-the-shelf reagents. Trim-Away allows the study of protein function in diverse cell types, including non-dividing primary cells where genome- and RNA-targeting methods are limited.

Original languageEnglish
Pages (from-to)1692-1706.e8
Number of pages34
JournalCell
Volume171
Issue number7
Early online date16 Nov 2017
DOIs
Publication statusPublished - 14 Dec 2017

Keywords

  • Journal Article

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