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Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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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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Canonical Wnt Signaling Pathway02:54

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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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Related Experiment Video

Updated: Jan 16, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
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Selective and Potent Peptide Binders of RNF43 for Wnt Signaling Inhibition.

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.

ACS Central Science
|September 29, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed novel peptides targeting Ring finger 43 (RNF43), a key regulator of Wnt signaling implicated in cancer. These tools enable RNF43 detection and inhibition, paving the way for new cancer therapies.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The Wnt/β-catenin pathway is crucial for human tumor progression.
  • Ring finger 43 (RNF43), a cell-surface E3 ubiquitin ligase, negatively regulates Wnt signaling by ubiquitylating the Frizzled co-receptor.
  • Inactivating mutations in RNF43 are linked to various cancers, underscoring its role in tumor biology, yet its precise mechanism remains unclear due to a lack of specific molecular tools.

Purpose of the Study:

  • To develop selective molecular tools for detecting and manipulating endogenous Ring finger 43 (RNF43).
  • To investigate the mechanism of RNF43 function and its role in Wnt signaling.
  • To explore the therapeutic potential of RNF43-targeting agents in cancer treatment.

Main Methods:

  • Design and synthesis of disulfide-constrained peptides with high affinity and specificity for RNF43.
  • Application of biotinylated peptides in immunofluorescence for RNF43 detection in intestinal crypts.
  • Integration of experimental and computational structural analyses to model peptide-RNF43 binding.
  • Generation of a hexavalent RNF43 binder (RNF43-DCP) to inhibit Wnt signaling.

Main Results:

  • A peptide, GUR-1.6.12.2, was identified with high affinity and specificity for RNF43.
  • RNF43 was successfully detected in intestinal crypts using biotinylated GUR-1.6.12.2 via immunofluorescence.
  • A structural model of GUR-1.6.12.2 binding to RNF43 was proposed.
  • The RNF43-DCP demonstrated inhibitory activity against Wnt signaling by competing with R-spondin.

Conclusions:

  • The developed RNF43 binders serve as valuable research tools for studying RNF43 activity.
  • These binders facilitate the investigation of RNF43's role in various biological contexts.
  • The RNF43-DCP shows potential as a therapeutic agent for targeting Wnt signaling in anticancer strategies.
  • This work offers new avenues for developing selective anticancer therapies focused on the Wnt pathway.