Evidence map›Paper›PMID 41524925›Full record

ArticleApoptosis : an international journal on programmed cell death2026

Activation of RIPK3 drives PANoptosis in human cells and inflammatory apoptosis in canine cells dependent on RIPK1, FADD and caspases.

Sarah M Worfolk, Noah J Phippen, Shayla G Verburg, Katrina A Kobal, Nicholas C Langelaan, Davier G Gongora, Jennifer Geddes-McAlister, Sarah K Wootton, Matthew S Miller, Samuel T Workenhe

Abstract read
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In one paragraph

Article in Apoptosis : an international journal on programmed cell death, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Sarah M WorfolkDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada.
Noah J PhippenDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada.
Shayla G VerburgDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada.
Katrina A KobalDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada.
Nicholas C LangelaanDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada.
Davier G GongoraDepartment of Molecular and Cellular Biology, College of Biological Sciences, University of Guelph, Guelph, ON, Canada.
Jennifer Geddes-McAlisterDepartment of Molecular and Cellular Biology, College of Biological Sciences, University of Guelph, Guelph, ON, Canada.
Sarah K WoottonDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada.
Matthew S MillerMichael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada.
Samuel T WorkenheDepartment of Pathobiology, Ontario Veterinary College, University of Guelph, 419 Gordon St. PAHL Bldg 89, room 4828, Guelph, ON, N1G 2W1, Canada. sworkenh@uoguelph.ca.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Programmed cell death in animal species of the order Carnivora is suspected to be unique due to the potential defects in activating the lytic cell death pathways, necroptosis and pyroptosis. In a wide range of species of the order Carnivora, including domestic cats and dogs, racoons, red foxes, and ferrets, the absence of the necroptosis executioner protein MLKL (mixed-lineage kinase domain-like pseudokinase) is suspected to prohibit necroptotic lysis. It remains unclear what type(s) of cell death are activated in canine cells downstream of RIPK3 (receptor-interacting protein kinase 3). Here, we show that activation of RIPK3 by expressing it with a trimerization domain drives PANoptosis in human fibroblasts but activates apoptosis in canine epithelial cells. Expression of trimerizable canine and human RIPK3 in canine cells activated apoptotic cell death dependent on caspases, FAS-associated death domain protein (FADD), and RIPK1. Human RIPK3 in canine cells activated a rapid apoptosis compared to the canine version. Unlike canonical caspase 8 driven apoptosis, RIPK3-driven canine cell apoptosis is associated with the secretion of danger-associated molecular patterns (DAMPs) and pro-inflammatory cytokines. This is the first study defining the function of canine RIPK3 and potentially immunostimulatory, non-lytic, cell death in canine cells. This form of cell death can be further developed to ignite immunity against virus infections and cancer.

Indexed as

ApoptosisCaspasesFas-Associated Death Domain ProteinInflammationNecroptosisReceptor-Interacting Protein Serine-Threonine KinasesAnimalsDogsFibroblastsHumansCaspasesFADD protein, humanFas-Associated Death Domain ProteinReceptor-Interacting Protein Serine-Threonine KinasesRIPK1 protein, humanRIPK3 protein, humanApoptosisCell deathDogNecroptosis

Identifiers

PMID41524925

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.