Cargando…
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-...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783300964832247808 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5818060 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT doldechristine ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT bischofjoachim ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT grutersimon ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT montadaanna ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT halekottejakob ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT peiferchristian ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT kalbacherhubert ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT baumannulrich ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT knippschilduwe ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT suterbeat ack1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT doldechristine ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT bischofjoachim ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT grutersimon ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT montadaanna ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT halekottejakob ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT peiferchristian ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT kalbacherhubert ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT baumannulrich ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT knippschilduwe ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e AT suterbeat ck1fretbiosensorrevealsthatddx3xisanessentialactivatorofck1e |