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Journal Article

A method for the acute and rapid degradation of endogenous proteins.

MPS-Authors
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Konieczny,  V.
Department of Meiosis, MPI for Biophysical Chemistry, Max Planck Society;

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Mogessie,  B.
Department of Meiosis, MPI for Biophysical Chemistry, Max Planck Society;

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Schuh,  M.
Department of Meiosis, MPI for Biophysical Chemistry, Max Planck Society;

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Fulltext (public)

2504062.pdf
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Supplementary Material (public)

2504062_Suppl_1.xlsx
(Supplementary material), 4MB

2504062_Suppl_2.xlsx
(Supplementary material), 4MB

2504062_Suppl_3.xlsx
(Supplementary material), 4MB

2504062_Suppl_4.mp4
(Supplementary material), 338KB

2504062_Suppl_5.mp4
(Supplementary material), 410KB

2504062_Suppl_6.mp4
(Supplementary material), 130KB

2504062_Suppl_7.mp4
(Supplementary material), 2MB

Citation

Clift, D., McEwan, W. A., Labzin, L. I., Konieczny, V., Mogessie, B., James, L. C., et al. (2017). A method for the acute and rapid degradation of endogenous proteins. Cell, 171(7), 1692-1706. doi:10.1016/j.cell.2017.10.033.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002E-3711-4
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.