ArticleeLife2019
Bim escapes displacement by BH3-mimetic anti-cancer drugs by double-bolt locking both Bcl-XL and Bcl-2.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Disruption of MCL1/BOK transmembrane interaction as a novel strategy to induce cell death in tumours.Cell death & disease · 2026Article
- Deciphering Bax Dynamics: Regulation, Retrotranslocation, and Mitochondrial Interplay in the Commitment to Apoptosis: A Narrative Review.Health science reports · 2026Article
- MTCH2 promotes BAX and BAK self-assembly and apoptotic pore growth.Nature structural & molecular biology · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Activator of apoptosis harakiri (HRK) localisation at mitochondria alters mitochondrial morphology independently of other BCL-2 proteins.The FEBS journal · 2026Article
- Multifaceted Roles of Bcl-2 Family Proteins: Regulatory Roles in Apoptosis, Physiological Functions, and Therapeutic Potential.Current medical science · 2025Review
- Allosteric regulation of BH3-in-groove interactions by tail anchors of BCL-xL complexes limits BH3 mimetic antagonism.Nature communications · 2025Article
- Targeting the BCL2 Family: Advances and Challenges in BH3 Mimetic-Based Therapies.International journal of molecular sciences · 2025Review
- Nesprin-2 contains BH3-like motifs that can promote cell death.Cell death discovery · 2025Article
- Bax- Bcl-xL interaction dynamics during the progression of cell cycle and cell death using FLIM-FRET.Cell stress · 2025Review
- Profiling protein-protein interactions to predict the efficacy of B-cell-lymphoma-2-homology-3 mimetics for acute myeloid leukaemia.Nature biomedical engineering · 2024Article
- BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains.EMBO reports · 2024Article
- The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.The Biochemical journal · 2024Review
- Polyamidoamine-Carbon Nanodot Conjugates with Bioreducible Building Blocks: Smart Theranostic Platforms for Targeted siRNA Delivery.Biomacromolecules · 2024Article
- Mitochondrial microproteins: critical regulators of protein import, energy production, stress response pathways, and programmed cell death.American journal of physiology. Cell physiology · 2023Review
- The carboxyl-terminal sequence of PUMA binds to both anti-apoptotic proteins and membranes.eLife · 2023Article
- Article
- Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol.Cell death and differentiation · 2022Article
- Pharmaceutical Reactivation of Attenuated Apoptotic Pathways Leads to Elimination of Osimertinib Drug-Tolerant Cells.Cancer research communications · 2022Article
- Efficacy and specificity of inhibitors of BCL-2 family protein interactions assessed by affinity measurements in live cells.Science advances · 2022Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Tumor initiation, progression and resistance to chemotherapy rely on cancer cells bypassing programmed cell death by apoptosis. We report that unlike other pro-apoptotic proteins, Bim contains two distinct binding sites for the anti-apoptotic proteins Bcl-XL and Bcl-2. These include the BH3 sequence shared with other pro-apoptotic proteins and an unexpected sequence located near the Bim carboxyl-terminus (residues 181-192). Using automated Fluorescence Lifetime Imaging Microscopy - Fluorescence Resonance Energy Transfer (FLIM-FRET) we show that the two binding interfaces enable Bim to double-bolt lock Bcl-XL and Bcl-2 in complexes resistant to displacement by BH3-mimetic drugs currently in use or being evaluated for cancer therapy. Quantifying in live cells the contributions of individual amino acids revealed that residue L185 previously thought involved in binding Bim to membranes, instead contributes to binding to anti-apoptotic proteins. This double-bolt lock mechanism has profound implications for the utility of BH3-mimetics as drugs. .
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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.