Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein

Shin-ichiro Hino; Shosei Kishida; Tatsuo Michiue; Akimasa Fukui; Ikuo Sakamoto; Shinji Takada; Makoto Asashima; Akira Kikuchi

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Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein

机译：一种新型的Dvl结合蛋白Idax对Wnt信号通路的抑制

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In attempting to clarify the roles of Dvl in the Wnt signaling pathway, we identified a novel protein which binds to the PDZ domain of Dvl and named it Idax (for inhibition of the Dvl and Axin complex). Idax and Axin competed with each other for the binding to Dvl. Immunocytochemical analyses showed that Idax was localized to the same place as Dvl in cells and that expression of Axin inhibited the colocalization of Dvl and Idax. Further, Wnt-induced accumulation of β-catenin and activation of T-cell factor in mammalian cells were suppressed by expression of Idax. Expression of Idax inXenopus embryos induced ventralization with a reduction in the expression of siamois, a Wnt-inducible gene. Idax inhibited Wnt- and Dvl- but not β-catenin-induced axis duplication. It is known that Dvl is a positive regulator in the Wnt signaling pathway and that the PDZ domain is important for this activity. Therefore, these results suggest that Idax functions as a negative regulator of the Wnt signaling pathway by directly binding to the PDZ domain of Dvl.

机译：在试图阐明Dvl在Wnt信号通路中的作用时，我们鉴定了一种与Dvl的PDZ结构域结合的新型蛋白质，并将其命名为Idax（用于抑制Dvl和Axin复合物）。 Idax和Axin相互竞争与Dvl的结合。免疫细胞化学分析显示Idax定位在细胞中与Dvl相同的位置，并且Axin的表达抑制了Dvl和Idax的共定位。此外，通过Idax的表达抑制了Wnt诱导的β-catenin的积累和T细胞因子在哺乳动物细胞中的活化。 Idax在非洲爪蟾胚胎中的表达诱导了腹侧受精，而Wnt诱导基因 siamois 的表达减少。 Idax抑制Wnt和Dvl-，但不抑制β-catenin诱导的轴重复。已知Dv1是Wnt信号传导途径中的正调节剂，并且PDZ结构域对该活性很重要。因此，这些结果表明，Idax通过直接结合至Dvl的PDZ结构域而充当Wnt信号传导途径的负调节剂。 展开▼

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《Molecular and Cellular Biology》 |2001年第1期|共13页

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Shin-ichiro Hino; Shosei Kishida; Tatsuo Michiue; Akimasa Fukui; Ikuo Sakamoto; Shinji Takada; Makoto Asashima; Akira Kikuchi;
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中图分类细胞生物学;

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专利

1. Identification and characterization of a novel Dvl-binding protein that suppresses Wnt signalling pathway. [J] . Oshita A, Kishida S, Kobayashi H, Genes to cells : . 2003,第12期

机译：鉴定和表征抑制Wnt信号通路的新型Dvl结合蛋白。

2. BMI1 activates WNT signaling in colon cancer by negatively regulating the WNT antagonist IDAX [J] . Yu Feiyue, Zhou Chuanyi, Zeng Hui, Biochemical and Biophysical Research Communications . 2018,第2期

机译：BMI1通过对WNT拮抗剂IDAX负面调节CONON癌中激活WNT信号传导

3. Effect of inhibition to Yes-related proteins-mediated Wnt/β-catenin signaling pathway through miR-195-5p on apoptosis of gastric cancer cells [J] . D.-L. Zhao, Q.-L. Wu European review for medical and pharmacological sciences. . 2019,第15期

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4. Inhibition of canonical Wnt signaling pathway by DKK1 induces increased ALP activity in hMSC in vitro [C] . Anna Thorfve, Anders Lindahl, Peter Thomsen, World biomaterials congress . 2012

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5. Crosstalk between G proteins and the canonical Wnt signaling pathway. [D] . Stemmle, Laura Nelson. 2005

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6. Effect of Huayu Tongluo Herbs on Reduction of Proteinuria via Inhibition of Wnt/β-Catenin Signaling Pathway in Diabetic Rats [O] . Lu Bai, Beibei Huo, Zhiqiang Chen, 2017

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7. Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein [O] . Hino, Shin-ichiro, Kishida, Shosei, Michiue, Tatsuo, 2001

机译：一种新型的Dvl结合蛋白Idax对Wnt信号通路的抑制

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4. Compounds derived from 3 - (imidazo 4,5-c pyridin-2-yl) - indazol, inhibitors of one or more proteins in the WNT signaling Pathway; Pharmaceutical Composition and method of treatment of a disorder or disease that is involved in the Aberrant WNT signaling such as cancer, osteoartriti S and Alzheimer's disease, among others. [P] . 外国专利： CL2014002511A1 . 2015-01-09

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Inhibition of the Wnt Signaling Pathway by Idax, a Novel Dvl-Binding Protein

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