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This page presents an AI-generated summary of a published research paper. The original authors did not write or review this article. [See full disclosure ↓]

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CASP5C amplifies Wnt signaling in human intestinal epithelium

Research area:Biochemistry, Genetics and Molecular BiologyMolecular BiologyInflammasome and immune disorders

What the study found

CASP5C, one of three CASP5 isoforms, is the form that uniquely promotes Wnt signaling in the human intestinal epithelium. The authors report that it does so by cleaving APC, a scaffold protein in the β-catenin destruction complex, which helps sustain intestinal epithelial renewal.

Why the authors say this matters

The authors conclude that CASP5C is an enzymatic amplifier of Wnt signaling that helps maintain proliferation of transit-amplifying cells, which are the Wnt-reliant offspring of intestinal stem cells. They also suggest that this broadens the role of inflammatory caspases beyond innate immunity and into tissue homeostasis.

What the researchers tested

The researchers examined CASP5 in human intestinal epithelial cells and organoids, including colonic and small intestinal organoids. They studied CASP5 isoforms, protein interactions, APC cleavage, and expression patterns in intestinal cells, injury, and inflammatory bowel disease.

What worked and what didn't

CASP5C, but not the other CASP5 isoforms, bound dishevelled, a protein that links Wnt receptors to the β-catenin destruction complex, through dishevelled's DEP domain. CASP5C cleaved APC at Asp556 and destabilized the β-catenin destruction complex, which enhanced Wnt signaling; endogenous and ectopic CASP5C also drove organoid growth, while CASP5A and CASP5B were more common in mature enterocytes.

What to keep in mind

The abstract does not describe specific experimental limitations or caveats. The findings are presented for human intestinal epithelium and organoid models, so the available summary does not state whether they apply beyond that context.

Key points

  • CASP5C is the CASP5 isoform that uniquely promotes Wnt signaling in human intestinal epithelium.
  • CASP5C cleaves APC at Asp556, which destabilizes the β-catenin destruction complex.
  • CASP5C binds dishevelled through its catalytic domain and dishevelled's DEP domain.
  • CASP5C expression peaks in transit-amplifying cells, while CASP5A and CASP5B predominate in mature enterocytes.
  • CASP5C drives growth of colonic and small intestinal organoids and is increased after epithelial injury and in inflammatory bowel disease.

Disclosure

Research title:
CASP5C amplifies Wnt signaling in human intestinal epithelium
Authors:
Baosen Jia, Yuhua Shi, Yourae Hong, Chongbo Yang, Dylan Roycroft, Shahida Kamal, Sushmita Mukherjee, Beatrix Ueberheide, Alex Grier, JRI Live cell bank, Ellen Scherl, D Lukin, R Longman, Vinita Jacob, Laura Sahyoun, Michael Mintz, Jennifer Claytor, Robbyn Sockolow, Aliza Solomon, Thomas Ciecierega, A. Bergman, Kimberley Chien, Kenny Joselin Castro Ochoa, E. E. Gordon, Lily Barash, Melissa Rose, Surgical GI, Kelly Garrett, Fabrizio Michelassi, Jeffrey Milsom, David Artis, Gregory Sonnenberg, LCB coordinator, Caitlin Mason, LCB processors, Victoria Ribeiro de Godoy, Adriana Brcic-Susak, Dario Garone, Chloe Scott, Lexi Tempera, Mavee Witherspoon, Maneeza Bilal, Bing He, Lauretta A. Lacko, Steven M. Lipkin, Sabine Tejpar, J. Magarian Blander
Institutions:
Cornell University, Cancer Research UK, KU Leuven, New York University, Universitair Ziekenhuis Leuven
Publication date:
2026-04-22
DOI:
10.1038/s41586-026-10343-8
OpenAlex record:
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AI provenance: This post was generated by OpenAI. The original authors did not write or review this post.

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