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A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε

Casein kinase 1 (CK1) plays central roles in various signal transduction pathways and performs many cellular activities. For many years CK1 was thought to act independently of modulatory subunits and in a constitutive manner. Recently, DEAD box RNA helicases, in particular DEAD box RNA helicase 3 X-...

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Autores principales: Dolde, Christine, Bischof, Joachim, Grüter, Simon, Montada, Anna, Halekotte, Jakob, Peifer, Christian, Kalbacher, Hubert, Baumann, Ulrich, Knippschild, Uwe, Suter, Beat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818060/
https://www.ncbi.nlm.nih.gov/pubmed/29222110
http://dx.doi.org/10.1242/jcs.207316
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author Dolde, Christine
Bischof, Joachim
Grüter, Simon
Montada, Anna
Halekotte, Jakob
Peifer, Christian
Kalbacher, Hubert
Baumann, Ulrich
Knippschild, Uwe
Suter, Beat
author_facet Dolde, Christine
Bischof, Joachim
Grüter, Simon
Montada, Anna
Halekotte, Jakob
Peifer, Christian
Kalbacher, Hubert
Baumann, Ulrich
Knippschild, Uwe
Suter, Beat
author_sort Dolde, Christine
collection PubMed
description Casein kinase 1 (CK1) plays central roles in various signal transduction pathways and performs many cellular activities. For many years CK1 was thought to act independently of modulatory subunits and in a constitutive manner. Recently, DEAD box RNA helicases, in particular DEAD box RNA helicase 3 X-linked (DDX3X), were found to stimulate CK1 activity in vitro. In order to observe CK1 activity in living cells and to study its interaction with DDX3X, we developed a CK1-specific FRET biosensor. This tool revealed that DDX3X is indeed required for full CK1 activity in living cells. Two counteracting mechanisms control the activity of these enzymes. Phosphorylation by CK1 impairs the ATPase activity of DDX3X and RNA destabilizes the DDX3X–CK1 complex. We identified possible sites of interaction between DDX3X and CK1. While mutations identified in the DDX3X genes of human medulloblastoma patients can enhance CK1 activity in living cells, the mechanism of CK1 activation by DDX3X points to a possible therapeutic approach in CK1-related diseases such as those caused by tumors driven by aberrant Wnt/β-catenin and Sonic hedgehog (SHH) activation. Indeed, CK1 peptides can reduce CK1 activity.
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spelling pubmed-58180602018-02-28 A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε Dolde, Christine Bischof, Joachim Grüter, Simon Montada, Anna Halekotte, Jakob Peifer, Christian Kalbacher, Hubert Baumann, Ulrich Knippschild, Uwe Suter, Beat J Cell Sci Research Article Casein kinase 1 (CK1) plays central roles in various signal transduction pathways and performs many cellular activities. For many years CK1 was thought to act independently of modulatory subunits and in a constitutive manner. Recently, DEAD box RNA helicases, in particular DEAD box RNA helicase 3 X-linked (DDX3X), were found to stimulate CK1 activity in vitro. In order to observe CK1 activity in living cells and to study its interaction with DDX3X, we developed a CK1-specific FRET biosensor. This tool revealed that DDX3X is indeed required for full CK1 activity in living cells. Two counteracting mechanisms control the activity of these enzymes. Phosphorylation by CK1 impairs the ATPase activity of DDX3X and RNA destabilizes the DDX3X–CK1 complex. We identified possible sites of interaction between DDX3X and CK1. While mutations identified in the DDX3X genes of human medulloblastoma patients can enhance CK1 activity in living cells, the mechanism of CK1 activation by DDX3X points to a possible therapeutic approach in CK1-related diseases such as those caused by tumors driven by aberrant Wnt/β-catenin and Sonic hedgehog (SHH) activation. Indeed, CK1 peptides can reduce CK1 activity. The Company of Biologists Ltd 2018-01-01 /pmc/articles/PMC5818060/ /pubmed/29222110 http://dx.doi.org/10.1242/jcs.207316 Text en © 2018. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Dolde, Christine
Bischof, Joachim
Grüter, Simon
Montada, Anna
Halekotte, Jakob
Peifer, Christian
Kalbacher, Hubert
Baumann, Ulrich
Knippschild, Uwe
Suter, Beat
A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
title A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
title_full A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
title_fullStr A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
title_full_unstemmed A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
title_short A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
title_sort ck1 fret biosensor reveals that ddx3x is an essential activator of ck1ε
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818060/
https://www.ncbi.nlm.nih.gov/pubmed/29222110
http://dx.doi.org/10.1242/jcs.207316
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