Role of DDX56 in GSK3β regulation during Wnt signaling
DDX RNA helicases are ATPases that promote RNA folding and processing in numerous biological processes and in disease. The function of most DDX helicases is still unknown. We have previously identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt/β-catenin network in embryonic development, where it acts as a regulatory subunit of Casein kinase 1 epsilon (CK1e). In the last funding period we have finalized a study (with I. Sinning (B07) and J. Krijgsveld (Z04) as coauthors), which indicates that unexpectedly, DDX proteins stimulate protein kinase activity by accelerating the exchange of ADP for ATP, commonly the rate-limiting step in protein phosphorylation. These findings reveal a novel, fundamental principle in kinase regulation. We have evidence that another kinase-DDX pair is engaged in Wnt signaling, namely GSK3b and DDX56. The three main aims of the project are to i) validate the interaction between DDX56 and GSK3b biochemically in the context of Wnt signaling in mammalian cultured cells; ii) demonstrate that DDX56 acts as NEF for GSK3b in vitro; iii) validate the interaction between DDX56 and GSK3b in the context of Wnt signaling during Xenopus development. This project will once again be carried out with I. Sinning (B07) and J. Krijgsveld (Z04) as close collaborators.
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