ArticleThe Journal of experimental medicine1999
Bcl-2-mediated drug resistance: inhibition of apoptosis by blocking nuclear factor of activated T lymphocytes (NFAT)-induced Fas ligand transcription.
Article in The Journal of experimental medicine, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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.
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.
Who cites it
56 citing papers in PubMed, 152 citations in OpenAlex.
- Mechanism-Based Strategies for Prevention of Taxane-Induced Hair Follicle Damage in Cancer Chemotherapy.Cancers · 2026Review
- Targeting NFAT2 for Reversing the P-gp-Mediated Multidrug Resistance to Paclitaxel by Manidipine.Cancers · 2025Article
- Role of SLC7A11/xCT in Ovarian Cancer.International journal of molecular sciences · 2024Review
- Transplant oncology and anti-cancer immunosuppressants.Frontiers in immunology · 2024Review
- Microtubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy.Advances in experimental medicine and biology · 2024Review
- Hyperprogression on anti-PD-1 treatment. Is subsequent therapy feasible? A case report and review of the literature.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2023Review
- Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Metformin Improves Ovarian Cancer Sensitivity to Paclitaxel and Platinum-Based Drugs: A Review of In Vitro Findings.International journal of molecular sciences · 2022Review
- Prime, shock and kill: BCL-2 inhibition for HIV cure.Frontiers in immunology · 2022Review
- Mechanisms of chemotherapy resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Roles of Nrf2 in Gastric Cancer: Targeting for Therapeutic Strategies.Molecules (Basel, Switzerland) · 2021Review
- Apoptotic Effects of Anthocyanins fromInternational journal of molecular sciences · 2021Article
- Key genes and drug delivery systems to improve the efficiency of chemotherapy.Cancer drug resistance (Alhambra, Calif.) · 2021Article
- Metabolic Remodelling: An Accomplice for New Therapeutic Strategies to Fight Lung Cancer.Antioxidants (Basel, Switzerland) · 2019Review
- Treatment effect and safety profile of salvage chemotherapy following immune checkpoint inhibitors in lung cancer.Lung cancer management · 2019Article
- MicroRNA-16 sensitizes drug-resistant breast cancer cells to Adriamycin by targeting Wip1 and Bcl-2.Oncology letters · 2019Article
- Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway.Oncology letters · 2019Article
- Article
- High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.Cell reports · 2019Article
- Bcl-2 Inhibition to Overcome Resistance to Chemo- and Immunotherapy.International journal of molecular sciences · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bcl-2 inhibits apoptosis induced by a variety of stimuli, including chemotherapy drugs and glucocorticoids. It is generally accepted that Bcl-2 exerts its antiapoptotic effects mainly by dimerizing with proapoptotic members of the Bcl-2 family such as Bax and Bad. However, the mechanism of the antiapoptotic effects is unclear. Paclitaxel and other drugs that disturb microtubule dynamics kill cells in a Fas/Fas ligand (FasL)-dependent manner; antibody to FasL inhibits paclitaxel-induced apoptosis. We have found that Bcl-2 overexpression leads to the prevention of chemotherapy (paclitaxel)-induced expression of FasL and blocks paclitaxel-induced apoptosis. The mechanism of this effect is that Bcl-2 prevents the nuclear translocation of NFAT (nuclear factor of activated T lymphocytes, a transcription factor activated by microtubule damage) by binding and sequestering calcineurin, a calcium-dependent phosphatase that must dephosphorylate NFAT to move to the nucleus. Without NFAT nuclear translocation, the FasL gene is not transcribed. Thus, it appears that paclitaxel and other drugs that disturb microtubule function kill cells at least in part through the induction of FasL. Furthermore, Bcl-2 antagonizes drug-induced apoptosis by inhibiting calcineurin activation, blocking NFAT nuclear translocation, and preventing FasL expression. The effects of Bcl-2 can be overcome, at least partially, through phosphorylation of Bcl-2. Phosphorylated Bcl-2 cannot bind calcineurin, and NFAT activation, FasL expression, and apoptosis can occur after Bcl-2 phosphorylation.
Indexed as
Identifiers
What OpenQuestion holds
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.