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Science 339 (6126): 1436-1441

Copyright © 2013 by the American Association for the Advancement of Science

RNA Helicase DDX3 Is a Regulatory Subunit of Casein Kinase 1 in Wnt–β-Catenin Signaling

Cristina-Maria Cruciat,1,* Christine Dolde,1,* Reinoud E. A. de Groot,2 Bisei Ohkawara,1,{dagger} Carmen Reinhard,1 Hendrik C. Korswagen,2 Christof Niehrs1,3,{ddagger}

Abstract: Casein kinase 1 (CK1) members play key roles in numerous biological processes. They are considered "rogue" kinases, because their enzymatic activity appears unregulated. Contrary to this notion, we have identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt–β-catenin network, where it acts as a regulatory subunit of CK1{varepsilon}: In a Wnt-dependent manner, DDX3 binds CK1{varepsilon} and directly stimulates its kinase activity, and promotes phosphorylation of the scaffold protein dishevelled. DDX3 is required for Wnt–β-catenin signaling in mammalian cells and during Xenopus and Caenorhabditis elegans development. The results also suggest that the kinase-stimulatory function extends to other DDX and CK1 members, opening fresh perspectives for one of the longest-studied protein kinase families.

1 Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
2 Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Netherlands.
3 Institute of Molecular Biology, D-55128 Mainz, Germany.

* These authors contributed equally to this work.

{dagger} Present address: Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Japan.

{ddagger} Corresponding author. E-mail: niehrs{at}dkfz-heidelberg.de


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