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

  • Dolde C Institute of Cell Biology, Department of Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.
  • Bischof J Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
  • Grüter S Institute of Cell Biology, Department of Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland.
  • Montada A Department of Chemistry, Institute of Biochemistry, University of Cologne, Otto-Fischer-Str. 12-14, 50674 Cologne, Germany.
  • Halekotte J Institute for Pharmaceutical Chemistry, Christian Albrechts University, Gutenbergstraße 76, 24118 Kiel, Germany.
  • Peifer C Institute for Pharmaceutical Chemistry, Christian Albrechts University, Gutenbergstraße 76, 24118 Kiel, Germany.
  • Kalbacher H Interfaculty Institute of Biochemistry, University of Tübingen, Ob dem Himmelreich 7, 72074 Tübingen, Germany.
  • Baumann U Department of Chemistry, Institute of Biochemistry, University of Cologne, Otto-Fischer-Str. 12-14, 50674 Cologne, Germany.
  • Knippschild U Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany.
  • Suter B Institute of Cell Biology, Department of Biology, University of Bern, Baltzerstrasse 4, 3012 Bern, Switzerland Beat.Suter@izb.unibe.ch.
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  • 2017-12-10
Published in:
  • Journal of cell science. - 2018
Activating kinase subunit
CK1 biosensor
Medulloblastoma
Protein Ser/Thr kinase
RNA helicase DDX3
Wnt signaling
Biosensing Techniques
Casein Kinase I
Cerebellar Neoplasms
DEAD-box RNA Helicases
Fluorescence Resonance Energy Transfer
Humans
Medulloblastoma
Mutation
Phosphorylation
RNA Helicases
Wnt Signaling Pathway
English 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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  • English
Open access status
hybrid
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https://sonar.ch/global/documents/201408
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