Kishida S, Yamamoto H, Hino S, Ikeda S, Kishida M, Kikuchi A.. DIX domains of Dvl and axin are necessary for protein interactions and their ability to regulate -catenin stability. Mol Cell Biol 19: 4414-4422

Department of Biochemistry, Hiroshima University School of Medicine, Minami-ku, Hiroshima 734-8551, Japan.
Molecular and Cellular Biology (Impact Factor: 4.78). 07/1999; 19(6):4414-22.
Source: PubMed


The N-terminal region of Dvl-1 (a mammalian Dishevelled homolog) shares 37% identity with the C-terminal region of Axin, and this related region is named the DIX domain. The functions of the DIX domains of Dvl-1 and Axin were investigated. By yeast two-hybrid screening, the DIX domain of Dvl-1 was found to interact with Dvl-3, a second mammalian Dishevelled relative. The DIX domains of Dvl-1 and Dvl-3 directly bound one another. Furthermore, Dvl-1 formed a homo-oligomer. Axin also formed a homo-oligomer, and its DIX domain was necessary. The N-terminal region of Dvl-1, including its DIX domain, bound to Axin directly. Dvl-1 inhibited Axin-promoted glycogen synthase kinase 3beta-dependent phosphorylation of beta-catenin, and the DIX domain of Dvl-1 was required for this inhibitory activity. Expression of Dvl-1 in L cells induced the nuclear accumulation of beta-catenin, and deletion of the DIX domain abolished this activity. Although expression of Axin in SW480 cells caused the degradation of beta-catenin and reduced the cell growth rate, expression of an Axin mutant that lacks the DIX domain did not affect the level of beta-catenin or the growth rate. These results indicate that the DIX domains of Dvl-1 and Axin are important for protein-protein interactions and that they are necessary for the ability of Dvl-1 and Axin to regulate the stability of beta-catenin.

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    • "The interaction of Dsh with Fz is known to be important for planar-cell polarity (reviewed in Seifert and Mlodzik, 2007), a non-canonical Wnt signaling process. Since Dsh also binds to Axin (Kishida et al., 1999; Smalley et al., 1999), Dsh-Fz interaction may facilitate recruitment of Axin to the Arrow/LRP cytosolic domain. This Axin movement could be a crucial event in pathway activation (Cliffe et al., 2003; Lee et al., 2003). "
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    • "This structure might contribute to make open interphase to bind to other proteins that are involved in abscission. As previously reported, Dvl oligomerizes via its DIX domain (Kishida et al., 1999; Schwarz-Romond et al., 2007), and therefore it is intriguing to speculate that oligomerization might be required for the structure formation and efficient stabilization of midbody microtubules. SIM image also revealed that Fz2 forms discontinuous ring structures at late telophase. "
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    Journal of Cell Science 07/2012; 125(20). DOI:10.1242/jcs.108142 · 5.43 Impact Factor
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    • "Dvl is considered to play a pivotal role in regulating WNT-activated signalling cascades. It has been shown that the DIX and PDZ domains trigger β-catenin stabilisation (Kishida et al., 1999), while the PDZ and DEP domains are required for activation of WNT noncanonical cascades. In the absence of WNT stimulation, β-catenin is retained in the cytoplasm by a multi-protein degradation complex comprising Glycogen synthase kinase 3 (GSK3) (Force and Woodgett, 2009) and Casein kinase 1a (CKI) (Bernatik et al., 2011), and two scaffold proteins, Adenomatous polyposis coli (APC) (Tanneberger et al., 2011) and Axin (Chia and Costantini, 2005). "
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