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

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

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Dolde C,Bischof J,Grüter S,Montada A,Halekotte J,Peifer C,Kalbacher H,Baumann U,Knippschild U,Suter B

doi

10.1242/jcs.207316

subject

Has Abstract

pub_date

2018-01-04 00:00:00

issue

1

eissn

0021-9533

issn

1477-9137

pii

jcs.207316

journal_volume

131

pub_type

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