Dolde, Christine, Bischof, Joachim, Gruter, Simon ORCID: 0000-0003-0124-8625, Montada, Anna, Halekotte, Jakob, Peifer, Christian, Kalbacher, Hubert, Baumann, Ulrich, Knippschild, Uwe and Suter, Beat (2018). A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1 epsilon. J. Cell Sci., 131 (1). CAMBRIDGE: COMPANY BIOLOGISTS LTD. ISSN 1477-9137

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Abstract

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/beta-catenin and Sonic hedgehog (SHH) activation. Indeed, CK1 peptides can reduce CK1 activity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Dolde, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bischof, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gruter, SimonUNSPECIFIEDorcid.org/0000-0003-0124-8625UNSPECIFIED
Montada, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halekotte, JakobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peifer, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kalbacher, HubertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumann, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knippschild, UweUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suter, BeatUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-204065
DOI: 10.1242/jcs.207316
Journal or Publication Title: J. Cell Sci.
Volume: 131
Number: 1
Date: 2018
Publisher: COMPANY BIOLOGISTS LTD
Place of Publication: CAMBRIDGE
ISSN: 1477-9137
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CASEIN KINASE 1; POTENT INHIBITORS; HELICASE DDX3X; I EPSILON; PHOSPHORYLATION; EXPRESSION; INITIATION; MUTATIONS; CK1-DELTA; DISTINCTMultiple languages
Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/20406

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