ReviewCell death and differentiation2014
The rheostat in the membrane: BCL-2 family proteins and apoptosis.
Review in Cell death and differentiation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 230 citations in OpenAlex.
- Role of Bcl-2 -938 C>A polymorphism in susceptibility and prognosis of cancer: a meta-analysis.Scientific reports · 2014Pooled it
- Prognostic model construction and drug prediction in colorectal cancer using mitochondrial programmed cell death-related genes.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- CUDC-907 inhibits glioblastoma and enhances glioblastoma sensitivity to temozolomide by inhibiting DNA damage repair.Genes & diseases · 2026Article
- Multifaceted Roles of Bcl-2 Family Proteins: Regulatory Roles in Apoptosis, Physiological Functions, and Therapeutic Potential.Current medical science · 2025Review
- Advances inMicroorganisms · 2025Review
- The Role of Functional Polymorphisms of ApoptoticIranian journal of medical sciences · 2025Article
- Article
- Nitrate protects against methotrexate-induced liver injury by activating Wnt/β-catenin Signaling in mice.Toxicology research · 2025Article
- Article
- Ferulic acid: extraction, estimation, bioactivity and applications for human health and food.Journal of the science of food and agriculture · 2025Review
- Optimizing Transmembrane Protein Assemblies in Nanodiscs for Structural Studies: A Comprehensive Manual.Bio-protocol · 2024Article
- The molecular anti-metastatic potential of CBD and THC from Lebanese Cannabis via apoptosis induction and alterations in autophagy.Scientific reports · 2024Article
- ADAM10 Alleviates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Activating the Notch Signaling Pathway.Cell biochemistry and biophysics · 2024Article
- Carbazole Derivatives Binding to Bcl-2 Promoter Sequence G-quadruplex.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Hexavalent Chromium Induces Neurotoxicity by Triggering Mitochondrial Dysfunction and ROS-Mediated Signals.Neurochemical research · 2024Article
- Ferulic acid suppresses the inflammation and apoptosis in Kawasaki disease through activating the AMPK/mTOR/NF-κB pathway.Frontiers in pharmacology · 2024Article
- Daphnoretin inhibits glioblastoma cell proliferation and metastasis via PI3K/AKT signaling pathway inactivation.Journal of Cancer · 2024Article
- An updated review of the pharmacological effects and potential mechanisms of hederagenin and its derivatives.Frontiers in pharmacology · 2024Review
- Co-administration with A1M does not influence apoptotic response ofScientific reports · 2023Article
- Cell Death Mechanisms in Cerebral Ischemia-Reperfusion Injury.Neurochemical research · 2022Review
47 more citing papers are in PubMed but not listed here.
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 2 institutions in 1 country.
Funding
Abstract
Apoptosis, a mechanism for programmed cell death, has key roles in human health and disease. Many signals for cellular life and death are regulated by the BCL-2 family proteins and converge at mitochondria, where cell fate is ultimately decided. The BCL-2 family includes both pro-life (e.g. BCL-XL) and pro-death (e.g. BAX, BAK) proteins. Previously, it was thought that a balance between these opposing proteins, like a simple 'rheostat', could control the sensitivity of cells to apoptotic stresses. Later, this rheostat concept had to be extended, when it became clear that BCL-2 family proteins regulate each other through a complex network of bimolecular interactions, some transient and some relatively stable. Now, studies have shown that the apoptotic circuitry is even more sophisticated, in that BCL-2 family interactions are spatially dynamic, even in nonapoptotic cells. For example, BAX and BCL-XL can shuttle between the cytoplasm and the mitochondrial outer membrane (MOM). Upstream signaling pathways can regulate the cytoplasmic-MOM equilibrium of BAX and thereby adjust the sensitivity of cells to apoptotic stimuli. Thus, we can view the MOM as the central locale of a dynamic life-death rheostat. BAX invariably forms extensive homo-oligomers after activation in membranes. However, recent studies, showing that activated BAX monomers determine the kinetics of MOM permeabilization (MOMP), perturb the lipid bilayer and form nanometer size pores, pose questions about the role of the oligomerization. Other lingering questions concern the molecular mechanisms of BAX redistribution between MOM and cytoplasm and the details of BAX/BAK-membrane assemblies. Future studies need to delineate how BCL-2 family proteins regulate MOMP, in concert with auxiliary MOM proteins, in a dynamic membrane environment. Technologies aimed at elucidating the structure and function of the full-length proteins in membranes are needed to illuminate some of these critical issues.
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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.