ArticleChemistry & biology2013
Multimodal interaction with BCL-2 family proteins underlies the proapoptotic activity of PUMA BH3.
Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- PUMA mediated afatinib-induced apoptosis in glioma cells.Archives of medical science : AMS · 2025Article
- Study of the Bcl-2 Interactome by BiFC Reveals Differences in the Activation Mechanism of Bax and Bak.Cells · 2023Article
- Drug resistance mechanism of kinase inhibitors in the treatment of hepatocellular carcinoma.Frontiers in pharmacology · 2023Review
- Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets.Journal of hematology & oncology · 2022Review
- Protein-protein and protein-lipid interactions of pore-forming BCL-2 family proteins in apoptosis initiation.Biochemical Society transactions · 2022Review
- Physiological and pharmacological modulation of BAX.Trends in pharmacological sciences · 2022Review
- BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Solution-State Preorganization of Cyclic β-Hairpin Ligands Determines Binding Mechanism and Affinities for MDM2.Journal of chemical information and modeling · 2021Article
- Eltrombopag directly inhibits BAX and prevents cell death.Nature communications · 2021Article
- Neuronal cell life, death, and axonal degeneration as regulated by the BCL-2 family proteins.Cell death and differentiation · 2021Review
- MiR-211 protects cerebral ischemia/reperfusion injury by inhibiting cell apoptosis.Bioengineered · 2020Article
- Characterization of an alternative BAK-binding site for BH3 peptides.Nature communications · 2020Article
- Homogeneous Oligomers of Pro-apoptotic BAX Reveal Structural Determinants of Mitochondrial Membrane Permeabilization.Molecular cell · 2020Article
- Hydrocarbon-Stitched Peptide Agonists of Glucagon-Like Peptide-1 Receptor.ACS chemical biology · 2020Article
- BAX, BAK, and BOK: A Coming of Age for the BCL-2 Family Effector Proteins.Cold Spring Harbor perspectives in biology · 2020Review
- The third model of Bax/Bak activation: a Bcl-2 family feud finally resolved?F1000Research · 2020Review
- Targeting BAX to drug death directly.Nature chemical biology · 2019Review
- Liposomal Permeabilization Assay to Study the Functional Interactions of the BCL-2 Family.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Topology of active, membrane-embedded Bax in the context of a toroidal pore.Cell death and differentiation · 2018Article
- BH3-Dependent and Independent Activation of BAX and BAK in Mitochondrial Apoptosis.Current opinion in physiology · 2018Article
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Authors and funding
7 authors.
Funding
Abstract
PUMA is a proapoptotic BCL-2 family member that drives the apoptotic response to a diversity of cellular insults. Deciphering the spectrum of PUMA interactions that confer its context-dependent proapoptotic properties remains a high priority goal. Here, we report the synthesis of PUMA SAHBs, structurally stabilized PUMA BH3 helices that, in addition to broadly targeting antiapoptotic proteins, directly bind to proapoptotic BAX. NMR, photocrosslinking, and biochemical analyses revealed that PUMA SAHBs engage an α1/α6 trigger site on BAX to initiate its functional activation. We further demonstrated that a cell-permeable PUMA SAHB analog induces apoptosis in neuroblastoma cells and, like expressed PUMA protein, engages BCL-2, MCL-1, and BAX. Thus, we find that PUMA BH3 is a dual antiapoptotic inhibitor and proapoptotic direct activator, and its mimetics may serve as effective pharmacologic triggers of apoptosis in resistant human cancers.
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