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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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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. |
format | Online Article Text |
id | pubmed-4961840 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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