The ankyrin repeat protein Diversin recruits Casein kinase Iε to the β-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling

By T. Schwarz‐Romond, C. Asbrand, J. Bakkers, Michael Kühl, H. Schaeffer, J. Huelsken, J. Behrens, M. Hammerschmidt, W. Birchmeier. 2002

171 citations recorded by the source corpus.

Wnt signals control decisive steps in development and can induce the formation of tumors. Canonical Wnt signals control the formation of the embryonic axis, and are mediated by stabilization and interaction of beta-catenin with Lef/Tcf transcription factors. An alternative branch of the Wnt pathway uses JNK to establish planar cell polarity in Drosophila and gastrulation movements in vertebrates. We describe here the vertebrate protein Diversin that interacts with two components of the canonical Wnt pathway, Casein kinase Iepsilon (CKIepsilon) and Axin/Conductin. Diversin recruits CKIepsilon to the beta-catenin degradation complex that consists of Axin/Conductin and GSK3beta and allows efficient phosphorylation of beta-catenin, thereby inhibiting beta-catenin/Tcf signals. Morpholino-based gene ablation in zebrafish shows that Diversin is crucial for axis formation, which depends on beta-catenin signaling. Diversin is also involved in JNK activation and gastrulation movements in zebrafish. Diversin is distantly related to Diego of Drosophila, which functions only in the pathway that controls planar cell polarity. Our data show that Diversin is an essential component of the Wnt-signaling pathway and acts as a molecular switch, which suppresses Wnt signals mediated by the canonical beta-catenin pathway and stimulates signaling via JNK.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/c9ffcc6455d038ccdcac34df7c142376647c7ed3

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In Molecular Biology

1. W. Birchmeier
2. B. Doble
3. J. Woodgett
4. Wenqing Xu
5. H. Varmus
6. Liang Schweizer
7. F. Cong
8. Konrad Basler

Citations in the corpus

• The circadian clock: pacemaker and tumour suppressor (2003, background): “Overexpression of CKIe mimics the effect of WNT signalling, resulting in cytoplasmic accumulation of β-catenin and its subsequent nuclear localizatio”
• Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways (2005, background): “Diversin inhibits canonical Wnt signaling and concomitantly controls gastrulation movements in zebrafish embryo”
• β-Catenin destruction complex: insights and questions from a structural perspective (2006, background): “One study has proposed that CK1e binds Axin indirectly via the protein Diversin (Schwarz-Romond et al., 2002), although the absence of an Axin-binding site in the Drosophila relative of Diversin (called Diego) indicates that this is not a conserved function between invertebrates and vertebrates.”
• GSK-3: tricks of the trade for a multi-tasking kinase (2003, background): “A novel ankyrin-repeatcontaining protein, Diversin, has been reported to recruit CKI to the destruction complex (Schwarz-Romond et al., 2002).”
• Deletion of β-catenin impairs T cell development (2003, background): “The Wnt signal inhibits the degradation of β-catenin by blocking its phosphorylation by casien kinase 1 and glycogen synthase kinase-3&beta”
• Casein Kinase Iε Modulates the Signaling Specificities of Dishevelled (2004, methodology): “Recently, it has been suggested that CKIe is recruited to the Axin–GSK3– -catenin complex by the ankyrin repeat protein Diversin ( 46 ).”