ArticleThe Journal of biological chemistry2016
Synthetic Antibodies Inhibit Bcl-2-associated X Protein (BAX) through Blockade of the N-terminal Activation Site.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- The potential of probiotic derivatives of Bacillus coagulans Hammer on induction of apoptosis in colorectal adenocarcinoma cell line in vitro.BMC complementary medicine and therapies · 2025Article
- Dexmedetomidine Suppresses Mitochondrial Autophagy and Apoptosis While Promoting Proliferation in Breast Cancer Cells in vitro via PI3K/AKT Signaling.Breast cancer (Dove Medical Press) · 2025Article
- Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.Acta pharmaceutica Sinica. B · 2024Review
- A novel inhibitory BAK antibody enables assessment of non-activated BAK in cancer cells.Cell death and differentiation · 2024Article
- Taurine alleviates high-fat-high-glucose-induced pancreatic islet β-cell oxidative stress and apoptosis in rat.Heliyon · 2023Article
- Mechanisms of BCL-2 family proteins in mitochondrial apoptosis.Nature reviews. Molecular cell biology · 2023Review
- Co-targeting of BAX and BCL-XL proteins broadly overcomes resistance to apoptosis in cancer.Nature communications · 2022Article
- Physiological and pharmacological modulation of BAX.Trends in pharmacological sciences · 2022Review
- Too much death can kill you: inhibiting intrinsic apoptosis to treat disease.The EMBO journal · 2021Review
- Lyciumamide A, a dimer of phenolic amide, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro.Journal of molecular histology · 2021Article
- Eltrombopag directly inhibits BAX and prevents cell death.Nature communications · 2021Article
- A small-molecule allosteric inhibitor of BAX protects against doxorubicin-induced cardiomyopathy.Nature cancer · 2020Article
- Pharmacological inhibition of Bax-induced cell death: Bax-inhibiting peptides and small compounds inhibiting Bax.Experimental biology and medicine (Maywood, N.J.) · 2019Review
- Small-molecule allosteric inhibitors of BAX.Nature chemical biology · 2019Article
- Isolation of Synthetic Antibodies Against BCL-2-Associated X Protein (BAX).Methods in molecular biology (Clifton, N.J.) · 2019Article
- Liposomal Permeabilization Assay to Study the Functional Interactions of the BCL-2 Family.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Interrogation of side chain biases for oligomannose recognition by antibody 2G12 via structure-guided phage display libraries.Bioorganic & medicinal chemistry · 2017Article
- Direct Activation of BAX by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia.Cancer cell · 2017Article
- Progress in targeting the BCL-2 family of proteins.Current opinion in chemical biology · 2017Review
- An Autoinhibited Dimeric Form of BAX Regulates the BAX Activation Pathway.Molecular cell · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The BCL-2 protein family plays a critical role in regulating cellular commitment to mitochondrial apoptosis. Pro-apoptotic Bcl-2-associated X protein (BAX) is an executioner protein of the BCL-2 family that represents the gateway to mitochondrial apoptosis. Following cellular stresses that induce apoptosis, cytosolic BAX is activated and translocates to the mitochondria, where it inserts into the mitochondrial outer membrane to form a toxic pore. How the BAX activation pathway proceeds and how this may be inhibited is not yet completely understood. Here we describe synthetic antibody fragments (Fabs) as structural and biochemical probes to investigate the potential mechanisms of BAX regulation. These synthetic Fabs bind with high affinity to BAX and inhibit its activation by the BH3-only protein tBID (truncated Bcl2 interacting protein) in assays using liposomal membranes. Inhibition of BAX by a representative Fab, 3G11, prevented mitochondrial translocation of BAX and BAX-mediated cytochrome c release. Using NMR and hydrogen-deuterium exchange mass spectrometry, we showed that 3G11 forms a stoichiometric and stable complex without inducing a significant conformational change on monomeric and inactive BAX. We identified that the Fab-binding site on BAX involves residues of helices α1/α6 and the α1-α2 loop. Therefore, the inhibitory binding surface of 3G11 overlaps with the N-terminal activation site of BAX, suggesting a novel mechanism of BAX inhibition through direct binding to the BAX N-terminal activation site. The synthetic Fabs reported here reveal, as probes, novel mechanistic insights into BAX inhibition and provide a blueprint for developing inhibitors of BAX activation.
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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.