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Tunable light and drug induced depletion of target proteins
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Journal Article
Tunable light and drug induced depletion of target proteins
2020
Overview
Biological processes in development and disease are controlled by the abundance, localization and modification of cellular proteins. We have developed versatile tools based on recombinant E3 ubiquitin ligases that are controlled by light or drug induced heterodimerization for nanobody or DARPin targeted depletion of endogenous proteins in cells and organisms. We use this rapid, tunable and reversible protein depletion for functional studies of essential proteins like PCNA in DNA repair and to investigate the role of CED-3 in apoptosis during
Caenorhabditis elegans
development. These independent tools can be combined for spatial and temporal depletion of different sets of proteins, can help to distinguish immediate cellular responses from long-term adaptation effects and can facilitate the exploration of complex networks.
Methods to control protein degradation usually require prior genetic engineering of each specific protein of interest. Here the authors present a toolbox for targeted depletion of endogenous proteins in cells and organisms, which is based on light- and drug-controlled recombinant E3 ubiquitin ligases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 14
/ 14/35
/ 14/63
/ 631/136
/ 631/1647
/ 631/80
/ Animals
/ Caenorhabditis elegans - genetics
/ Caenorhabditis elegans - metabolism
/ Caenorhabditis elegans Proteins - drug effects
/ Caenorhabditis elegans Proteins - genetics
/ Caenorhabditis elegans Proteins - metabolism
/ Caenorhabditis elegans Proteins - radiation effects
/ Caspases - radiation effects
/ DNA
/ DNA-Binding Proteins - metabolism
/ Gene Expression Regulation, Developmental
/ Humanities and Social Sciences
/ Humans
/ Light
/ Proliferating cell nuclear antigen
/ Proliferating Cell Nuclear Antigen - metabolism
/ Proteins
/ Science
/ Transcription Factors - metabolism
/ Ubiquitin-Protein Ligases - drug effects
/ Ubiquitin-Protein Ligases - genetics
