ArticleThe EMBO journal2012
Caspase-2 is an initiator caspase responsible for pore-forming toxin-mediated apoptosis.
Article in The EMBO journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 88 citations in OpenAlex.
- Acidic and alkaline conditions enhance Staphylococcus aureus α-toxin pore formation and cytotoxicity.PLoS pathogens · 2026Article
- The Calcium-Calpain-ALIX Axis is the Major Link Between Gasdermin-D Membrane Pores and Terminal Membrane Damage in Pyroptosis.Research square · 2026Article
- 17β-estradiol and estrogen receptor alpha protect mouse ovarian follicle development by repressing atresia.iScience · 2025Article
- Ally or traitor: the dual role of p62 in caspase-2 regulation.Cell death & disease · 2024Article
- Apoptosis Inhibitor 5: A Multifaceted Regulator of Cell Fate.Biomolecules · 2024Review
- ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2.The EMBO journal · 2023Article
- Triglyceride induces DNA damage leading to monocyte death by activating caspase-2 and caspase-8.BMB reports · 2023Article
- Reprogramming of Cell Death Pathways by Bacterial Effectors as a Widespread Virulence Strategy.Infection and immunity · 2022Review
- The caspase-2 substrate p54nrb exhibits a multifaceted role in tumor cell death susceptibility via gene regulatory functions.Cell death & disease · 2022Article
- Article
- The IRE1α Stress Signaling Axis Is a Key Regulator of Neutrophil Antimicrobial Effector Function.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- The p53-caspase-2 axis in the cell cycle and DNA damage response.Experimental & molecular medicine · 2021Review
- Article
- Antiapoptotic Clone 11-Derived Peptides InduceJournal of virology · 2020Article
- The Role of Caspase-2 in Regulating Cell Fate.Cells · 2020Review
- Manipulation of Autophagy and Apoptosis Facilitates Intracellular Survival ofFrontiers in immunology · 2020Article
- Selective Host Cell Death byFrontiers in immunology · 2020Review
- The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis.International review of cell and molecular biology · 2020Review
- Host-Targeted Therapeutics against Multidrug Resistant IntracellularAntibiotics (Basel, Switzerland) · 2019Review
- Intracellular Staphylococcus aureus Modulates Host Central Carbon Metabolism To Activate Autophagy.mSphere · 2018Article
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 6 countries.
Funding
Abstract
Bacterial pathogens modulate host cell apoptosis to establish a successful infection. Pore-forming toxins (PFTs) secreted by pathogenic bacteria are major virulence factors and have been shown to induce various forms of cell death in infected cells. Here we demonstrate that the highly conserved caspase-2 is required for PFT-mediated apoptosis. Despite being the second mammalian caspase to be identified, the role of caspase-2 during apoptosis remains enigmatic. We show that caspase-2 functions as an initiator caspase during Staphylococcus aureus α-toxin- and Aeromonas aerolysin-mediated apoptosis in epithelial cells. Downregulation of caspase-2 leads to a strong inhibition of PFT-mediated apoptosis. Activation of caspase-2 is PIDDosome-independent, and endogenous caspase-2 is recruited to a high-molecular-weight complex in α-toxin-treated cells. Interestingly, prevention of PFT-induced potassium efflux inhibits the formation of caspase-2 complex, leading to its inactivation, thus resisting apoptosis. These results revealed a thus far unknown, obligatory role for caspase-2 as an initiator caspase during PFT-mediated apoptosis.
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Registered trials
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.