BACKGROUND: Dvl is a cytoplasmic protein to regulate the stability of beta-catenin in the Wnt signalling pathway. However, the molecular mechanism by which Dvl regulates the Wnt signalling pathway is not fully understood. RESULTS: We identified a novel protein that binds to Dvl and named it Daple. Daple consisted of 2009 amino acids with a high frequency of leucine residues and formed a homo-oligomer. The C-terminal three amino acids of Daple were necessary for binding to the region containing the PDZ domain of Dvl. Expression of Daple in mouse fibroblast L cells inhibited Wnt-3a-induced accumulation of beta-catenin. Furthermore, Daple inhibited Wnt-3a-dependent activation of T-cell factor (Tcf) transcriptional activity. Expression of Daple in the dorsal region of Xenopus embryos inhibited axis formation, which is known to be regulated by the Wnt signalling pathway. Daple also inhibited Dvl-induced secondary axis formation in Xenopus embryos. CONCLUSIONS: Daple binds to Dvl and functions as a negative regulator of the Wnt signalling pathway.
BACKGROUND:Dvl is a cytoplasmic protein to regulate the stability of beta-catenin in the Wnt signalling pathway. However, the molecular mechanism by which Dvl regulates the Wnt signalling pathway is not fully understood. RESULTS: We identified a novel protein that binds to Dvl and named it Daple. Daple consisted of 2009 amino acids with a high frequency of leucine residues and formed a homo-oligomer. The C-terminal three amino acids of Daple were necessary for binding to the region containing the PDZ domain of Dvl. Expression of Daple in mouse fibroblast L cells inhibited Wnt-3a-induced accumulation of beta-catenin. Furthermore, Daple inhibited Wnt-3a-dependent activation of T-cell factor (Tcf) transcriptional activity. Expression of Daple in the dorsal region of Xenopus embryos inhibited axis formation, which is known to be regulated by the Wnt signalling pathway. Daple also inhibited Dvl-induced secondary axis formation in Xenopus embryos. CONCLUSIONS:Daple binds to Dvl and functions as a negative regulator of the Wnt signalling pathway.
Authors: A B Ekici; D Hilfinger; M Jatzwauk; C T Thiel; D Wenzel; I Lorenz; E Boltshauser; T W Goecke; G Staatz; D J Morris-Rosendahl; H Sticht; U Hehr; A Reis; A Rauch Journal: Mol Syndromol Date: 2010-09-14
Authors: Joshua F Robinson; Zachariah Guerrette; Xiaozhong Yu; Sungwoo Hong; Elaine M Faustman Journal: Birth Defects Res B Dev Reprod Toxicol Date: 2010-06
Authors: Anthony Leyme; Arthur Marivin; Marcin Maziarz; Vincent DiGiacomo; Maria P Papakonstantinou; Prachi P Patel; Juan B Blanco-Canosa; Isha A Walawalkar; Gonzalo Rodriguez-Davila; Isabel Dominguez; Mikel Garcia-Marcos Journal: Proc Natl Acad Sci U S A Date: 2017-11-13 Impact factor: 11.205
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