ArticleThe Journal of biological chemistry2015
Mouse cytotoxic T cell-derived granzyme B activates the mitochondrial cell death pathway in a Bim-dependent fashion.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Drug-tolerant persisters and immunotherapy persister cells exhibit cross-resistance and share common survival mechanisms.Cell death and differentiation · 2026Article
- Identifying Negative Biomarkers of CD4 Cytotoxic T Lymphocytes via Granzyme B Exclusion Analysis.European journal of immunology · 2026Article
- Engineered CAR-T-Derived Exosomes Co-Delivering miR-145 and Cytotoxic Proteins for Targeted Solid Tumour Therapy.Journal of extracellular vesicles · 2026Article
- Unraveling key genes and mitochondrial-related mechanisms of atherosclerosis severity: explorations based on interpretable machine learning.BMC cardiovascular disorders · 2026Article
- Mutant calreticulin enables potent and selective CAR-T cell therapy in preclinical models of myeloproliferative neoplasms.Journal for immunotherapy of cancer · 2026Article
- Donor-Derived Vγ9Vδ2 T Cells for Acute Myeloid Leukemia: A Promising "Off-the-Shelf" Immunotherapy Approach.Cancers · 2025Article
- Selective Detection of Active Extracellular Granzyme A by Using a Novel Fluorescent Immunoprobe with Application to Inflammatory Diseases.ACS pharmacology & translational science · 2024Article
- Gasdermins in sepsis.Frontiers in immunology · 2023Review
- Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance.Journal of clinical medicine · 2022Review
- Targeting the Microenvironment for Treating Multiple Myeloma.International journal of molecular sciences · 2022Review
- All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity.Frontiers in immunology · 2022Review
- Escaping Death: How Cancer Cells and Infected Cells Resist Cell-Mediated Cytotoxicity.Frontiers in immunology · 2022Review
- Review
- Cell death induced by cytotoxic CD8Journal for immunotherapy of cancer · 2020Article
- Inhibition of Lung Tumor Development in ApoE Knockout Mice via Enhancement of TREM-1 Dependent NK Cell Cytotoxicity.Frontiers in immunology · 2019Article
- T Cells and Regulated Cell Death: Kill or Be Killed.International review of cell and molecular biology · 2019Review
- Mannose-6-phosphate receptor: a novel regulator of T cell immunity.Cellular & molecular immunology · 2018Review
- Identification of differentially expressed miRNAs in alopecia areata that target immune-regulatory pathways.Genes and immunity · 2017Article
- Positive and negative functions of B lymphocytes in tumors.Oncotarget · 2016Review
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxic T cells (Tc) use perforin and granzyme B (gzmB) to kill virus-infected cells and cancer cells. Recent evidence suggests that human gzmB primarily induces apoptosis via the intrinsic mitochondrial pathway by either cleaving Bid or activating Bim leading to the activation of Bak/Bax and subsequent generation of active caspase-3. In contrast, mouse gzmB is thought to predominantly induce apoptosis by directly processing pro-caspase-3. However, in certain mouse cell types gzmB-mediated apoptosis mainly occurs via the mitochondrial pathway. To investigate whether Bim is involved under the latter conditions, we have now employed ex vivo virus-immune mouse Tc that selectively kill by using perforin and gzmB (gzmB(+)Tc) as effector cells and wild type as well as Bim- or Bak/Bax-deficient spontaneously (3T9) or virus-(SV40) transformed mouse embryonic fibroblast cells as targets. We show that gzmB(+)Tc-mediated apoptosis (phosphatidylserine translocation, mitochondrial depolarization, cytochrome c release, and caspase-3 activation) was severely reduced in 3T9 cells lacking either Bim or both Bak and Bax. This outcome was related to the ability of Tc cells to induce the degradation of Mcl-1 and Bcl-XL, the anti-apoptotic counterparts of Bim. In contrast, gzmB(+)Tc-mediated apoptosis was not affected in SV40-transformed mouse embryonic fibroblast cells lacking Bak/Bax. The data provide evidence that Bim participates in mouse gzmB(+)Tc-mediated apoptosis of certain targets by activating the mitochondrial pathway and suggest that the mode of cell death depends on the target cell. Our results suggest that the various molecular events leading to transformation and/or immortalization of cells have an impact on their relative resistance to the multiple gzmB(+)Tc-induced death pathways.
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