ArticleThe Journal of experimental medicine2000
Apoptotic protease activating factor 1 (Apaf-1)-independent cell death suppression by Bcl-2.
Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 159 citations in OpenAlex.
- Evasion of cell death despite mitochondrial outer membrane permeabilization: an oncogenic outcome of apoptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- A metabolic cell death program downstream of SARM1 couples NADProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis.BMC molecular and cell biology · 2024Article
- Mitochondrial E3 ubiquitin ligase MARCHF5 controls BAK apoptotic activity independently of BH3-only proteins.Cell death and differentiation · 2023Article
- Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network.Biomolecules · 2022Review
- The Role of PKC and HIF-1 and the Effect of Traditional Chinese Medicinal Compounds on Cerebral Ischemia-Reperfusion Injury.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Effects of fluorodeoxyglucose magnetic nanoparticles on NCI-H727 and SH-SY5Y cancer cells.Asian journal of nanoscience and materials · 2021Article
- Targeting apoptotic caspases in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Intratumor Heterogeneity and Therapy Resistance: Contributions of Dormancy, Apoptosis Reversal (Anastasis) and Cell Fusion to Disease Recurrence.International journal of molecular sciences · 2020Review
- Mitochondrial inner membrane permeabilisation enables mtDNA release during apoptosis.The EMBO journal · 2018Article
- MOMP, cell suicide as a BCL-2 family business.Cell death and differentiation · 2018Review
- Cap-Independent Translational Control of Carcinogenesis.Frontiers in oncology · 2016Review
- MiR-1188 at the imprinted Dlk1-Dio3 domain acts as a tumor suppressor in hepatoma cells.Molecular biology of the cell · 2015Article
- The effects of erdosteine and N-acetylcysteine on apoptotic and antiapoptotic markers in pulmonary epithelial cells in sepsis.The Eurasian journal of medicine · 2013Article
- GAPDH binds to active Akt, leading to Bcl-xL increase and escape from caspase-independent cell death.Cell death and differentiation · 2013Article
- Prognostic value of LIPC in non-small cell lung carcinoma.Cell cycle (Georgetown, Tex.) · 2013Article
- The mitochondrial dynamics of Alzheimer's disease and Parkinson's disease offer important opportunities for therapeutic intervention.Current pharmaceutical design · 2011Article
- Mitochondria and cell death: outer membrane permeabilization and beyond.Nature reviews. Molecular cell biology · 2010Review
- Galangin induces apoptosis of hepatocellular carcinoma cells via the mitochondrial pathway.World journal of gastroenterology · 2010Article
- Resistance to caspase-independent cell death requires persistence of intact mitochondria.Developmental cell · 2010Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Reportedly, antiapoptotic Bcl-2 family proteins suppress apoptosis by binding to and inhibiting members of the CED-4 family of caspase activators. To explore this question, we used embryonic stem (ES) cells in which one (-/+) or both (-/-) copies of the gene encoding apoptotic protease activating factor 1 (Apaf-1), a CED-4 homologue, were disrupted by homologous recombination. Stable clones of heterozygous (-/+) and homozygous (-/-) Apaf-1 knockout ES cells that overexpressed Bcl-2 were generated. Withdrawal of serum growth factors or stimulation of heterozygous ES cells with staurosporine (STS), ultraviolet (UV)B irradiation, etoposide (VP16), or cisplatin induced apoptosis followed by cell death (determined by failure to exclude propidium iodide dye). These cell death stimuli also induced activation of several types of caspases and loss of mitochondrial membrane potential (DeltaPsi) in heterozygous (+/-) Apaf-1 knockout ES cells. In addition, overexpression of Bcl-2 protected against these events in Apaf-1-expressing ES cells. In contrast, STS, UVB, and VP16 induced little or no caspase activation and apoptosis in homozygous (-/-) Apaf-1 knockout ES cells. Nevertheless, Apaf-1-deficient ES cells subjected to these cell death stimuli or deprived of growth factors did eventually die through a nonapoptotic mechanism associated with loss of DeltaPsi. Moreover, Bcl-2 overprotection preserved DeltaPsi, reduced the percentage of Apaf-1(-/)- ES cells undergoing cell death, and increased clonigenic survival. The extent of Bcl-2-mediated cytoprotection was not significantly different for heterozygous (-/+) versus homozygous (-/-) Apaf-1 knockout cells. Furthermore, although Bcl-2 could be readily coimmunoprecipitated with Bax, associations with Apaf-1 were undetectable under conditions where Apaf-1 interactions with procaspase-9 were observed. We conclude that Bcl-2 has cytoprotective functions independent of Apaf-1, preserving mitochondrial function through a caspase-independent mechanism.
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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.