A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε
| Autor: | Christine Dolde, Joachim Bischof, Ulrich Baumann, Beat Suter, Simon Grüter, Anna Montada, Hubert Kalbacher, Christian Peifer, Jakob Halekotte, Uwe Knippschild |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
DEAD box Activating kinase subunit Biosensing Techniques Protein Ser/Thr kinase DEAD-box RNA Helicases 03 medical and health sciences Fluorescence Resonance Energy Transfer Humans Sonic hedgehog RNA helicase DDX3 Phosphorylation Cerebellar Neoplasms Wnt Signaling Pathway biology Casein Kinase I Wnt signaling pathway RNA CK1 biosensor Cell Biology RNA Helicase A Wnt signaling Cell biology 030104 developmental biology Mutation biology.protein 570 Life sciences Casein kinase 1 Signal transduction RNA Helicases Research Article Medulloblastoma |
| Zdroj: | Dolde, Christine; Bischof, Joachim; Grüter, Simon; Montada, Anna; Halekotte, Jakob; Peifer, Christian; Kalbacher, Hubert; Baumann, Ulrich; Knippschild, Uwe; Suter, Beat (2018). A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1ε. Journal of cell science, 131(1) Company of Biologists Limited 10.1242/jcs.207316 Journal of Cell Science |
| DOI: | 10.7892/boris.112039 |
| Popis: | 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. Highlighted Article: A FRET biosensor reveals DDX3X as an essential activator of the CK1 kinase in living cells. Its CK1-activating function is counteracted by its ATPase activity and also by CK1 peptides. |
| Databáze: | OpenAIRE |
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