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Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

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 results in tumor...

Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

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 results in tumor...

Non-Canonical Wnt Signaling Pathways

Non-Canonical Wnt Signaling Pathways

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...

Non-Canonical Wnt Signaling Pathways

Non-Canonical Wnt Signaling Pathways

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...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...

The Proteasome

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...

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Related Experiment Video

Updated: Jun 27, 2026

The Soft Agar Colony Formation Assay

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

Wnt-induced proteolytic targeting.

Katherine A Jones¹, Caroline R Kemp

¹Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. jones@salk.edu

Genes & Development

|December 6, 2008

Summary

This summary is machine-generated.

Wnt signaling drives mammary tumors by inducing the Cul4A E3 ligase. This ligase targets the p27Kip1 protein for degradation, revealing a new Wnt-induced cancer mechanism.

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Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Published on: June 17, 2014

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Last Updated: Jun 27, 2026

The Soft Agar Colony Formation Assay

The Soft Agar Colony Formation Assay

Published on: October 27, 2014

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Reconstitution Of β-catenin Degradation In Xenopus Egg Extract

Published on: June 17, 2014

Area of Science:

Oncology
Molecular Biology
Biochemistry

Background:

Aberrant Wnt pathway signaling is a significant driver of various cancers, particularly primary breast cancers.
The cyclin-dependent kinase inhibitor p27(Kip1) plays a crucial role in cell cycle regulation and tumor suppression.

Discussion:

This study identifies the Cul4A E3 ligase as the exclusive enzyme responsible for the ubiquitylation and proteasomal degradation of p27(Kip1) in Wnt10b-induced mammary tumors.
Wnt signaling strongly induces the expression of Cul4A, linking Wnt activity directly to the regulation of p27(Kip1) stability.

Key Insights:

A novel Wnt-induced proteolytic targeting system involving Cul4A and p27(Kip1) has been discovered.
This mechanism highlights a new pathway through which Wnt signaling promotes mammary tumorigenesis.

Outlook:

Understanding this Wnt-induced degradation pathway offers potential therapeutic targets for Wnt-driven cancers.
Further research into the Cul4A E3 ligase and its substrates could elucidate broader roles in cancer development.