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Phenotypes on demand via switchable target protein degradation in multicellular organisms
Phenotypes on demand via switchable target protein degradation in multicellular organisms
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Phenotypes on demand via switchable target protein degradation in multicellular organisms
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Phenotypes on demand via switchable target protein degradation in multicellular organisms
Phenotypes on demand via switchable target protein degradation in multicellular organisms

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Phenotypes on demand via switchable target protein degradation in multicellular organisms
Phenotypes on demand via switchable target protein degradation in multicellular organisms
Journal Article

Phenotypes on demand via switchable target protein degradation in multicellular organisms

2016
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Overview
Phenotypes on-demand generated by controlling activation and accumulation of proteins of interest are invaluable tools to analyse and engineer biological processes. While temperature-sensitive alleles are frequently used as conditional mutants in microorganisms, they are usually difficult to identify in multicellular species. Here we present a versatile and transferable, genetically stable system based on a low-temperature-controlled N-terminal degradation signal (lt-degron) that allows reversible and switch-like tuning of protein levels under physiological conditions in vivo. Thereby, developmental effects can be triggered and phenotypes on demand generated. The lt-degron was established to produce conditional and cell-type-specific phenotypes and is generally applicable in a wide range of organisms, from eukaryotic microorganisms to plants and poikilothermic animals. We have successfully applied this system to control the abundance and function of transcription factors and different enzymes by tunable protein accumulation. Switching target protein accumulation and activity by portable conditional degrons is potentially useful for both basic research and bioengineering. Here the authors present a versatile system to tune protein levels in live animals and plants using a temperature-sensitive N-end rule degradation signal.