ArticleProceedings of the National Academy of Sciences of the United States of America1997
Channel formation by antiapoptotic protein Bcl-2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.
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Who cites it
132 citing papers in PubMed, 604 citations in OpenAlex.
- Impact of BCL-2 rs2279115 and rs3943258 variants on protein expression and clinical outcome of urothelial bladder carcinoma.Molecular biology reports · 2026Article
- Current status, hotspots and frontiers of ion channel-related research in glioblastoma: a bibliometric analysis from 2005 to 2024.Frontiers in oncology · 2025Review
- A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C.Cell death and differentiation · 2023Article
- Markedly divergent effects of Ouabain on a Temozolomide-resistant (T98G) vs. a Temozolomide-sensitive (LN229) Glioblastoma cell line.Discover oncology · 2023Article
- Mitochondrial ion channels in pancreatic β-cells: Novel pharmacological targets for the treatment of Type 2 diabetes.British journal of pharmacology · 2021Review
- Neutron reflectometry and NMR spectroscopy of full-length Bcl-2 protein reveal its membrane localization and conformation.Communications biology · 2021Article
- A Glimpse of Programmed Cell Death Among Bacteria, Animals, and Plants.Frontiers in cell and developmental biology · 2021Review
- BCL-2 family isoforms in apoptosis and cancer.Cell death & disease · 2019Review
- Flupirtine derivatives as potential treatment for the neuronal ceroid lipofuscinoses.Annals of clinical and translational neurology · 2018Article
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- Apoptosis in inner ear sensory hair cells.Journal of otology · 2017Review
- Augmentation of the cytotoxic effects of zinc oxide nanoparticles by MTCP conjugation: Non-canonical apoptosis and autophagy induction in human adenocarcinoma breast cancer cell lines.Materials science & engineering. C, Materials for biological applications · 2017Article
- Redox Control of Multidrug Resistance and Its Possible Modulation by Antioxidants.Oxidative medicine and cellular longevity · 2016Review
- How do viruses control mitochondria-mediated apoptosis?Virus research · 2015Review
- Membrane Repair: Mechanisms and Pathophysiology.Physiological reviews · 2015Review
- Why do we study animal toxins?Dong wu xue yan jiu = Zoological research · 2015Review
- Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport.Scientific reports · 2015Article
- Mitochondria and apoptosis: emerging concepts.F1000prime reports · 2015Review
- Bioactive lipids and the control of Bax pro-apoptotic activity.Cell death & disease · 2014Review
- A recombined protein (rSj16) derived from Schistosoma japonicum induces cell cycle arrest and apoptosis of murine myeloid leukemia cells.Parasitology research · 2013Article
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Bcl-2 is the prototypical member of a large family of apoptosis-regulating proteins, consisting of blockers and promoters of cell death. The three-dimensional structure of a Bcl-2 homologue, Bcl-XL, suggests striking similarity to the pore-forming domains of diphtheria toxin and the bacterial colicins, prompting exploration of whether Bcl-2 is capable of forming pores in lipid membranes. Using chloride efflux from KCl-loaded unilamellar lipid vesicles as an assay, purified recombinant Bcl-2 protein exhibited pore-forming activity with properties similar to those of the bacterial toxins, diphtheria toxin, and colicins, i.e., dependence on low pH and acidic lipid membranes. In contrast, a mutant of Bcl-2 lacking the two core hydrophobic alpha-helices (helices 5 and 6), predicted to be required for membrane insertion and channel formation, produced only nonspecific effects. In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. The most frequent conductance observed (18 +/- 2 pS in 0.5 M KCl at pH 7.4) is consistent with a four-helix bundle structure arising from Bcl-2 dimers. However, larger channel conductances (41 +/- 2 pS and 90 +/- 10 pS) also were detected with progressively lower occurrence, implying the step-wise formation of larger oligomers of Bcl-2 in membranes. These findings thus provide biophysical evidence that Bcl-2 forms channels in lipid membranes, suggesting a novel function for this antiapoptotic protein.
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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.