B01

Role of DDX56 in GSK3ß regulation during Wnt signaling

Funding period: 2017-2025

Project B01

Project Leaders

Prof. Dr. Christof Niehrs

Prof. Dr. Christof Niehrs

 Project Leader B01

Abstract

We have previously identified the DEAD-box RNA helicase DDX3 as a regulator of the Wnt/β-catenin network in embryonic development, where it stimulates Casein kinase 1 epsilon (CK1e). Our unpublished work indicates that other members of the 44 DEAD-box RNA helicases can also function as kinase regulators in Wnt signaling. Here we will focus on DDX56 and its role in GSK3β regulation during Wnt signaling in mammalian cells and in early Xenopus embryonic development.

Project-related Publications

R-Spondin 2 governs Xenopus left-right body axis formation by establishing an FGF signaling gradient

Lee H, Camuto CM, Niehrs C. Nat Commun. 2024 Feb 2;15(1):1003. doi: 10.1038/s41467-024-44951-7. PMID: 38307837

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ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation

Sun R, Meng Z, Lee H, Offringa R, Niehrs C. Cell Chem Biol. 2023 Jun 8:S2451-9456(23)00153-8. doi: 10.1016/j.chembiol.2023.05.010. Online ahead of print. PMID: 37321224

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DEAD box RNA helicases act as nucleotide exchange factors for casein kinase 2

Fatti E, Hirth A, Švorinić A, Günther M, Stier G, Cruciat CM, Acebrón SP, Papageorgiou D, Sinning I, Krijgsveld J, Höfer T, Niehrs C. Sci Signal. 2023 Apr 25;16(782):eabp8923. doi: 10.1126/scisignal.abp8923. Epub 2023 Apr 25. PMID: 37098120

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Mucociliary Wnt signaling promotes cilia biogenesis and beating

Seidl C, Da Silva F, Zhang K, Wohlgemuth K, Omran H, Niehrs C. Nat Commun. 2023 Mar 6;14(1):1259. doi: 10.1038/s41467-023-36743-2. PMID: 36878953

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Primary cilia are WNT-transducing organelles whose biogenesis is controlled by a WNT-PP1 axis

Zhang K, Da Silva F, Seidl C, Wilsch-Bräuninger M, Herbst J, Huttner WB, Niehrs C. Dev Cell. 2023 Jan 23;58(2):139-154.e8. doi: 10.1016/j.devcel.2022.12.006. PMID: 36693320

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Uncoupling the BMP receptor antagonist function from the WNT agonist function of R-spondin 2 using the inhibitory peptide dendrimer RWd

Lee H, Sun R, Niehrs C. J Biol Chem. 2022 Jan 12:101586. doi: 10.1016/j.jbc.2022.101586. Online ahead of print.
PMID: 35032551

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The role of Xenopus developmental biology in unraveling Wnt signalling and antero-posterior axis formation

Niehrs C. Dev Biol. 2022 Feb;482:1-6. doi: 10.1016/j.ydbio.2021.11.006. Epub 2021 Nov 21. PMID: 34818531

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A MET-PTPRK kinase-phosphatase rheostat controls ZNRF3 and Wnt signaling

Kim M, Reinhard C, Niehrs C. Elife. 2021 Sep 30;10:e70885. doi: 10.7554/eLife.70885.
PMID: 34590584

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RSPO2 inhibits BMP signaling to promote self-renewal in acute myeloid leukemia

Sun R, He L, Lee H, Glinka A, Andresen C, Hübschmann D, Jeremias I, Müller-Decker K, Pabst C, Niehrs C. Cell Rep. 2021 Aug 17;36(7):109559. doi: 10.1016/j.celrep.2021.109559.
PMID: 34407399

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R-spondins are BMP receptor antagonists in Xenopus early embryonic development

Lee H, Seidl C, Sun R, Glinka A, Niehrs C. Nat Commun. 2020 Nov 4;11(1):5570. 

PMID: 33149137

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The tumor suppressor PTPRK promotes ZNRF3 internalization and is required for Wnt inhibition in the Spemann organizer

Chang LS, Kim M, Glinka A, Reinhard C, Niehrs C. Elife. 2020 Jan 14;9. pii: e51248. PMID: 31934854

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Cancer cell specific inhibition of Wnt/β-catenin signaling by forced intracellular acidification

Melnik S, Dvornikov D, Müller-Decker K, Depner S, Stannek P, Meister M, Warth A, Thomas M, Muley T, Risch A, Plass C, Klingmüller U, Niehrs C, Glinka A. Cell Discov. 2018 Jul 3;4:37. PMID: 29977599

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Angiopoietin-like 4 Is a Wnt Signaling Antagonist that Promotes LRP6 Turnover

Kirsch N, Chang LS, Koch S, Glinka A, Dolde C, Colozza G, Benitez MDJ, De Robertis EM, Niehrs C. Dev Cell. 2017 Oct 9;43(1):71-82.e6. doi: 10.1016/j.devcel.2017.09.011. PMID: 29017031

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Posttranscriptional Wnt signaling governs epididymal sperm maturation

Koch S, Acebron SP, Herbst J, Hatiboglu G, Niehrs C. Cell. 2015 Nov 19;163(5):1225-1236. doi: 10.1016/j.cell.2015.10.029. PMID: 26590424

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Maternal Wnt/STOP signaling promotes cell division during early Xenopus embryogenesis

Huang YL, Anvarian Z, Döderlein G, Acebron SP, Niehrs C. Proc Natl Acad Sci U S A. 2015 May 5;112(18):5732-7. doi: 10.1073/pnas.1423533112. Epub 2015 Apr 21. PMID: 25901317

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Mitotic wnt signaling promotes protein stabilization and regulates cell size

Acebron SP, Karaulanov E, Berger BS, Huang YL, Niehrs C. Mol Cell. 2014 May 22;54(4):663-74. doi: 10.1016/j.molcel.2014.04.014. Epub 2014 May 15. PMID: 24837680

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RNA helicase DDX3 is a regulatory subunit of casein kinase 1 in Wnt-beta-catenin signaling

Cruciat CM, Dolde C, de Groot RE, Ohkawara B, Reinhard C, Korswagen HC, Niehrs C. Science. 2013 Mar 22;339(6126):1436-41. doi: 10.1126/science.1231499. Epub 2013 Feb 14.
PMID: 23413191

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Cell cycle control of wnt receptor activation

Davidson G, Shen J, Huang YL, Su Y, Karaulanov E, Bartscherer K, Hassler C, Stannek P, Boutros M, Niehrs C. Dev Cell. 2009 Dec;17(6):788-99. doi: 10.1016/j.devcel.2009.11.006. PMID: 20059949

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Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation

Bilic J, Huang YL, Davidson G, Zimmermann T, Cruciat CM, Bienz M, Niehrs C. Science. 2007 Jun 15;316(5831):1619-22. doi: 10.1126/science.1137065.
PMID: 17569865

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Casein kinase 1 gamma couples Wnt receptor activation to cytoplasmic signal transduction

Davidson G, Wu W, Shen J, Bilic J, Fenger U, Stannek P, Glinka A, Niehrs C. Nature. 2005 Dec 8;438(7069):867-72. doi: 10.1038/nature04170.
PMID: 16341016

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