4.8 Article

Phenotypes on demand via switchable target protein degradation in multicellular organisms

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Nature Communications
卷 7, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms12202

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  1. EMBO Young Investigator Programme (YIP)
  2. Action Thematique et Incitative sur Programme (ATIP) from the Centre National de la Recherche Scientifique (CNRS)
  3. state of Saxony Anhalt
  4. Deutsche Forschungsgemeinschaft (DFG), Graduate Training Center GRK1026 'Conformational Transitions in Macromolecular Interactions' at Halle
  5. Leibniz Institute of Plant Biochemistry (IPB) at Halle, Germany
  6. Open Access fund of the Leibniz Association

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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.

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