title: Phenotypes on demand via switchable target protein degradation in multicellular organisms.
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.
authors.affiliation: Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB), Weinberg 3, D-06120 Halle (Saale), Germany.|ScienceCampus Halle-Plant-based Bioeconomy, Betty-Heimann-Strasse 3, D-06120 Halle (Saale), Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Faden
authors.affiliation: University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory, Carl-von-Linné-Weg 10, D-50829 Cologne, Germany.|University of Cologne, Institute of Botany III, Biocenter, Zülpicher Str. 47 b, D-50674 Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Ramezani
authors.affiliation: Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB), Weinberg 3, D-06120 Halle (Saale), Germany.|ScienceCampus Halle-Plant-based Bioeconomy, Betty-Heimann-Strasse 3, D-06120 Halle (Saale), Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mielke
authors.affiliation: Institute of Molecular Systems Biology (IMSB), Swiss Federal Institute of Technology (ETH), Wolfgang-Pauli-Strasse 16, CH-8093 Zurich, Switzerland.
authors.forename: Isabel
authors.initials: I
authors.lastname: Almudi
authors.affiliation: Institute of Molecular Systems Biology (IMSB), Swiss Federal Institute of Technology (ETH), Wolfgang-Pauli-Strasse 16, CH-8093 Zurich, Switzerland.
authors.forename: Knud
authors.initials: K
authors.lastname: Nairz
authors.affiliation: Institute for Genetics, Biocenter, University of Cologne, Zülpicher Straße 47a, D-50674 Cologne, Germany.
authors.forename: Marceli S
authors.initials: MS
authors.lastname: Froehlich
authors.affiliation: Institute for Genetics, Biocenter, University of Cologne, Zülpicher Straße 47a, D-50674 Cologne, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Höckendorff
authors.affiliation: Computational Chemistry, Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry (IPB), Weinberg 3, D-06120 Halle (Saale), Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brandt
authors.affiliation: Proteomics Unit, Leibniz Institute of Plant Biochemistry (IPB), Weinberg 3, Halle (Saale) D-06120, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoehenwarter
authors.affiliation: Institute for Genetics, Biocenter, University of Cologne, Zülpicher Straße 47a, D-50674 Cologne, Germany.
authors.forename: R Jürgen
authors.initials: RJ
authors.lastname: Dohmen
authors.affiliation: University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory, Carl-von-Linné-Weg 10, D-50829 Cologne, Germany.|University of Cologne, Institute of Botany III, Biocenter, Zülpicher Str. 47 b, D-50674 Cologne, Germany.|Département Mécanismes Moléculaires de la Plasticité Phénotypique, Institut de Biologie Moléculaire des Plantes du CNRS, IBMP-CNRS, Unité Propre de Recherche 2357, Conventionné avec l'Université de Strasbourg, 12, rue du Général Zimmer, Strasbourg F-67000, France.
authors.forename: Arp
authors.initials: A
authors.lastname: Schnittger
authors.affiliation: Independent Junior Research Group on Protein Recognition and Degradation, Leibniz Institute of Plant Biochemistry (IPB), Weinberg 3, D-06120 Halle (Saale), Germany.|ScienceCampus Halle-Plant-based Bioeconomy, Betty-Heimann-Strasse 3, D-06120 Halle (Saale), Germany.|University Group at the Max Planck Institute for Plant Breeding Research (MPIPZ), Max Delbrück Laboratory, Carl-von-Linné-Weg 10, D-50829 Cologne, Germany.|University of Cologne, Institute of Botany III, Biocenter, Zülpicher Str. 47 b, D-50674 Cologne, Germany.|Département Mécanismes Moléculaires de la Plasticité Phénotypique, Institut de Biologie Moléculaire des Plantes du CNRS, IBMP-CNRS, Unité Propre de Recherche 2357, Conventionné avec l'Université de Strasbourg, 12, rue du Général Zimmer, Strasbourg F-67000, France.
authors.forename: Nico
authors.initials: N
authors.lastname: Dissmeyer
mesh_terms: D000818:Animals; D017360:Arabidopsis / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004330:Drosophila / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D059748:Proteolysis; D012441:Saccharomyces cerevisiae / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D013045:Species Specificity; D013696:Temperature; D014026:Nicotiana / Q000145:classification / Q000235:genetics / Q000378:metabolism*