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CASP5C promotes Wnt signaling in human intestinal epithelium

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Research area:biology-genetics

What the study found

The study found that caspase 5 is restricted to the human intestinal epithelium and that one isoform, CASP5C, uniquely promotes Wnt signaling. The authors report that CASP5C cleaves APC, a scaffold protein in the β-catenin destruction complex, and 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, the Wnt-reliant progeny of intestinal stem cells, as the Wnt gradient declines. They also say these findings broaden the roles of inflammatory caspases beyond innate immunity and into tissue homeostasis.

What the researchers tested

The researchers examined CASP5 expression and isoforms in human intestinal epithelial cells and organoids. They studied protein interactions in colonic epithelial cells, including binding between CASP5 and dishevelled, and tested how CASP5C affects APC cleavage, Wnt signaling, and organoid growth.

What worked and what didn't

CASP5C, but not the other CASP5 isoforms, was linked to increased Wnt signaling. The abstract says CASP5C binds dishevelled through its catalytic domain, cleaves APC at Asp556, destabilizes the β-catenin destruction complex, and drives growth of colonic and small intestinal organoids. CASP5A and CASP5B predominated in mature enterocytes, while CASP5C peaked in transit-amplifying cells and was selectively induced after intestinal epithelial injury and increased in inflammatory bowel disease.

What to keep in mind

The summary does not describe experimental limitations in detail. The findings are presented for human intestinal epithelium, so the scope in the abstract is specific to that tissue and species.

Key points

  • CASP5 is restricted to the human intestinal epithelium.
  • CASP5C is the isoform that uniquely promotes Wnt signaling.
  • CASP5C cleaves APC at Asp556 and destabilizes the β-catenin destruction complex.
  • CASP5C peaks in transit-amplifying cells, while CASP5A and CASP5B predominate in mature enterocytes.
  • CASP5C is selectively induced after intestinal epithelial injury and is increased in inflammatory bowel disease.

Disclosure

Research title:
CASP5C promotes 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, Elliott 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:
Cancer Research UK, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, Cornell University, KU Leuven, 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 gpt-5.4-mini (OpenAI). The original authors did not write or review this post.

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