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相关概念视频

Non-Canonical Wnt Signaling Pathways01:41

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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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相关实验视频

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RNF43的选择性和强大的结剂用于Wnt信号抑制.

Sunhee Hwang1, Paula Flórez Salcedo1, Antonion Korcari1

  • 1Departments of †Peptide Therapeutics, ‡Regenerative Medicine, §Structural Biology, ∥Small Molecule Analytical Chemistry and Quality Control, ⊥Microchemistry, Proteomics and Lipidomics, Genentech Inc., South San Francisco, California 94080, United States.

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概括

研究人员开发了针对Ring finger 43 (RNF43) 的新,这是Wnt信号传递的关键调节器,与癌症有关. 这些工具可以检测和抑制RNF43,为新的癌症疗法铺平道路.

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科学领域:

  • 在瘤学瘤学.
  • 分子生物学分子生物学
  • 生物化学 生物化学

背景情况:

  • Wnt/β-catenin通路对于人类瘤进展至关重要.
  • 环指43 (RNF43),一个细胞表面E3泛素结合酶,通过使Frizzled共同受体无处不在来负面调节Wnt信号传递.
  • 无活化RNF43突变与各种癌症有关,强调其在瘤生物学中的作用,但由于缺乏特定的分子工具,其精确的机制仍然不清楚.

研究的目的:

  • 开发选择性分子工具来检测和操纵内源性环指43 (RNF43).
  • 研究RNF43功能的机制及其在Wnt信号传输中的作用.
  • 探索RNF43向剂在癌症治疗中的治疗潜力.

主要方法:

  • 设计和合成二硫化物受约束,对RNF43.4具有高度亲和力和特异性.
  • 生物化在免疫光中的应用,用于在肠道密室中检测RNF43.
  • 实验和计算结构分析的整合以建模-RNF43结合.
  • 生成一个六价RNF43结合剂 (RNF43-DCP) 来抑制Wnt信号传输.

主要成果:

  • 鉴定出一种,GUR-1.6.12.2,对RNF43.4具有很高的亲和力和特异性.
  • 通过免疫光检测成功检测到RNF43在肠道密室使用生物化GUR-1.6.12.2.
  • 提出了GUR-1.6.12.2与RNF43结合的结构模型.
  • 通过与R-spondin竞争,RNF43-DCP显示出对Wnt信号的抑制活性.

结论:

  • 开发的RNF43结合剂作为研究RNF43活性的有价值的研究工具.
  • 这些结合剂有助于研究RNF43在各种生物环境中的作用.
  • 在抗癌策略中,RNF43-DCP显示出作为向Wnt信号的治疗剂的潜力.
  • 这项工作为开发针对Wnt途径的选择性抗癌疗法提供了新的途径.