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Phenotypes on demand via switchable target protein degradation in multicellular organisms

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 identif...

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Autores principales: Faden, Frederik, Ramezani, Thomas, Mielke, Stefan, Almudi, Isabel, Nairz, Knud, Froehlich, Marceli S., Höckendorff, Jörg, Brandt, Wolfgang, Hoehenwarter, Wolfgang, Dohmen, R. Jürgen, Schnittger, Arp, Dissmeyer, Nico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961840/
https://www.ncbi.nlm.nih.gov/pubmed/27447739
http://dx.doi.org/10.1038/ncomms12202
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author Faden, Frederik
Ramezani, Thomas
Mielke, Stefan
Almudi, Isabel
Nairz, Knud
Froehlich, Marceli S.
Höckendorff, Jörg
Brandt, Wolfgang
Hoehenwarter, Wolfgang
Dohmen, R. Jürgen
Schnittger, Arp
Dissmeyer, Nico
author_facet Faden, Frederik
Ramezani, Thomas
Mielke, Stefan
Almudi, Isabel
Nairz, Knud
Froehlich, Marceli S.
Höckendorff, Jörg
Brandt, Wolfgang
Hoehenwarter, Wolfgang
Dohmen, R. Jürgen
Schnittger, Arp
Dissmeyer, Nico
author_sort Faden, Frederik
collection PubMed
description 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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spelling pubmed-49618402016-09-06 Phenotypes on demand via switchable target protein degradation in multicellular organisms Faden, Frederik Ramezani, Thomas Mielke, Stefan Almudi, Isabel Nairz, Knud Froehlich, Marceli S. Höckendorff, Jörg Brandt, Wolfgang Hoehenwarter, Wolfgang Dohmen, R. Jürgen Schnittger, Arp Dissmeyer, Nico Nat Commun Article 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. Nature Publishing Group 2016-07-22 /pmc/articles/PMC4961840/ /pubmed/27447739 http://dx.doi.org/10.1038/ncomms12202 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Faden, Frederik
Ramezani, Thomas
Mielke, Stefan
Almudi, Isabel
Nairz, Knud
Froehlich, Marceli S.
Höckendorff, Jörg
Brandt, Wolfgang
Hoehenwarter, Wolfgang
Dohmen, R. Jürgen
Schnittger, Arp
Dissmeyer, Nico
Phenotypes on demand via switchable target protein degradation in multicellular organisms
title Phenotypes on demand via switchable target protein degradation in multicellular organisms
title_full Phenotypes on demand via switchable target protein degradation in multicellular organisms
title_fullStr Phenotypes on demand via switchable target protein degradation in multicellular organisms
title_full_unstemmed Phenotypes on demand via switchable target protein degradation in multicellular organisms
title_short Phenotypes on demand via switchable target protein degradation in multicellular organisms
title_sort phenotypes on demand via switchable target protein degradation in multicellular organisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4961840/
https://www.ncbi.nlm.nih.gov/pubmed/27447739
http://dx.doi.org/10.1038/ncomms12202
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