ArticleProceedings of the National Academy of Sciences of the United States of America2020
Mcl-1 and Bok transmembrane domains: Unexpected players in the modulation of apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Disruption of MCL1/BOK transmembrane interaction as a novel strategy to induce cell death in tumours.Cell death & disease · 2026Article
- Proteasome inhibition enhances lysosome-mediated targeted protein degradation.Cell death & disease · 2026Article
- SARS-CoV-2 membrane protein biogenesis.bioRxiv : the preprint server for biology · 2026Article
- The roles of mitochondria in global and local intracellular calcium signalling.Nature reviews. Molecular cell biology · 2025Review
- Article
- BRD-810 is a highly selective MCL1 inhibitor with optimized in vivo clearance and robust efficacy in solid and hematological tumor models.Nature cancer · 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
- Review
- Phenotyping of cancer-associated somatic mutations in the BCL2 transmembrane domain.Oncogenesis · 2024Article
- Mechanisms of BCL-2 family proteins in mitochondrial apoptosis.Nature reviews. Molecular cell biology · 2023Review
- Article
- Machine Learning-Driven Multiscale Modeling: Bridging the Scales with a Next-Generation Simulation Infrastructure.Journal of chemical theory and computation · 2023Article
- Computational design of BclxL inhibitors that target transmembrane domain interactions.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Apoptotic mitochondrial poration by a growing list of pore-forming BCL-2 family proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Bok: real killer or bystander with non-apoptotic roles?Frontiers in cell and developmental biology · 2023Review
- Understanding MCL1: from cellular function and regulation to pharmacological inhibition.The FEBS journal · 2022Review
- A review on cullin neddylation and strategies to identify its inhibitors for cancer therapy.3 Biotech · 2022Article
- Endogenous Bok is stable at the endoplasmic reticulum membrane and does not mediate proteasome inhibitor-induced apoptosis.Frontiers in cell and developmental biology · 2022Article
- Conformational Clamping by a Membrane Ligand Activates the EphA2 Receptor.Journal of molecular biology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Bcl-2 protein family comprises both pro- and antiapoptotic members that control the permeabilization of the mitochondrial outer membrane, a crucial step in the modulation of apoptosis. Recent research has demonstrated that the carboxyl-terminal transmembrane domain (TMD) of some Bcl-2 protein family members can modulate apoptosis; however, the transmembrane interactome of the antiapoptotic protein Mcl-1 remains largely unexplored. Here, we demonstrate that the Mcl-1 TMD forms homooligomers in the mitochondrial membrane, competes with full-length Mcl-1 protein with regards to its antiapoptotic function, and induces cell death in a Bok-dependent manner. While the Bok TMD oligomers locate preferentially to the endoplasmic reticulum (ER), heterooligomerization between the TMDs of Mcl-1 and Bok predominantly takes place at the mitochondrial membrane. Strikingly, the coexpression of Mcl-1 and Bok TMDs produces an increase in ER mitochondrial-associated membranes, suggesting an active role of Mcl-1 in the induced mitochondrial targeting of Bok. Finally, the introduction of Mcl-1 TMD somatic mutations detected in cancer patients alters the TMD interaction pattern to provide the Mcl-1 protein with enhanced antiapoptotic activity, thereby highlighting the clinical relevance of Mcl-1 TMD interactions.
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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.