Phenotypes on demand via switchable target protein degradation in multicellular organisms

Frederik Faden, Thomas Ramezani, Stefan Mielke, Isabel Almudi, Knud Nairz, Marceli S. Froehlich, Jörg Höckendorff, Wolfgang Brandt, Wolfgang Hoehenwarter, R. Jürgen Dohmen, Arp Schnittger and Nico Dissmeyer ()
Additional contact information
Frederik Faden: Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB)
Thomas Ramezani: University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory
Stefan Mielke: Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB)
Isabel Almudi: Institute of Molecular Systems Biology (IMSB), Swiss Federal Institute of Technology (ETH)
Knud Nairz: Institute of Molecular Systems Biology (IMSB), Swiss Federal Institute of Technology (ETH)
Marceli S. Froehlich: Institute for Genetics, Biocenter, University of Cologne
Jörg Höckendorff: Institute for Genetics, Biocenter, University of Cologne
Wolfgang Brandt: Computational Chemistry, Leibniz Institute of Plant Biochemistry (IPB)
Wolfgang Hoehenwarter: Proteomics Unit, Leibniz Institute of Plant Biochemistry (IPB)
R. Jürgen Dohmen: Institute for Genetics, Biocenter, University of Cologne
Arp Schnittger: University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory
Nico Dissmeyer: Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB)

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms12202

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