ArticleThe EMBO journal2018
Dimer-specific immunoprecipitation of active caspase-2 identifies TRAF proteins as novel activators.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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.
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.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- TNK1 is a targetable JAK-independent driver of STAT signaling and inflammation.Genes & development · 2026Article
- Low-dose TNF-α drives malignant progression and lipid metabolism in glioblastoma through the TRAF2-FASN axis.Cell death discovery · 2026Article
- Pan-cancer analysis shows that TNFSF4 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including liver cancer.BMC cancer · 2025Article
- Ally or traitor: the dual role of p62 in caspase-2 regulation.Cell death & disease · 2024Article
- Chemoproteomics Identifies State-Dependent and Proteoform-Selective Caspase-2 Inhibitors.Journal of the American Chemical Society · 2024Article
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- Review
- Thymoquinone Alterations of the Apoptotic Gene Expressions and Cell Cycle Arrest in Genetically Distinct Triple-Negative Breast Cancer Cells.Nutrients · 2022Article
- Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis.Oncogene · 2022Article
- K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR.Cell death & disease · 2021Article
- Structural feature of TRAFs, their related human diseases and therapeutic intervention.Archives of pharmacal research · 2021Review
- Cryptotanshinone Ameliorates Doxorubicin-Induced Cardiotoxicity by Targeting Akt-GSK-3β-mPTP Pathway In Vitro.Molecules (Basel, Switzerland) · 2021Article
- Comparison of Target Recognition by TRAF1 and TRAF2.International journal of molecular sciences · 2020Article
- Caspase-2 Substrates: To Apoptosis, Cell Cycle Control, and Beyond.Frontiers in cell and developmental biology · 2020Review
- Roles of TRAFs in Ischemia-Reperfusion Injury.Frontiers in cell and developmental biology · 2020Review
- Caspase-2 promotes AMPA receptor internalization and cognitive flexibility via mTORC2-AKT-GSK3β signaling.Nature communications · 2019Article
- miR-214 Down-Regulation Promoted Hypoxia/Reoxygenation-Induced Hepatocyte Apoptosis Through TRAF1/ASK1/JNK Pathway.Digestive diseases and sciences · 2019Article
- Condemned or Not to Die? Gene Polymorphisms Associated With Cell Death in Pemphigus Foliaceus.Frontiers in immunology · 2019Article
- A Conserved Requirement forFrontiers in physiology · 2019Article
- CD137 (4-1BB) Signalosome: Complexity Is a Matter of TRAFs.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Caspase-2 has been shown to initiate apoptotic cell death in response to specific intracellular stressors such as DNA damage. However, the molecular mechanisms immediately upstream of its activation are still poorly understood. We combined a caspase-2 bimolecular fluorescence complementation (BiFC) system with fluorophore-specific immunoprecipitation to isolate and study the active caspase-2 dimer and its interactome. Using this technique, we found that tumor necrosis factor receptor-associated factor 2 (TRAF2), as well as TRAF1 and 3, directly binds to the active caspase-2 dimer. TRAF2 in particular is necessary for caspase-2 activation in response to apoptotic cell death stimuli. Furthermore, we found that dimerized caspase-2 is ubiquitylated in a TRAF2-dependent manner at K15, K152, and K153, which in turn stabilizes the active caspase-2 dimer complex, promotes its association with an insoluble cellular fraction, and enhances its activity to fully commit the cell to apoptosis. Together, these data indicate that TRAF2 positively regulates caspase-2 activation and consequent cell death by driving its activation through dimer-stabilizing ubiquitylation.
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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.