ArticleOncotarget2016
The trans-membrane domain of Bcl-2α, but not its hydrophobic cleft, is a critical determinant for efficient IP3 receptor inhibition.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 37 citations in OpenAlex.
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- BCL-2 and BOK regulate apoptosis by interaction of their C-terminal transmembrane domains.EMBO reports · 2024Article
- Calcium's Role in Orchestrating Cancer Apoptosis: Mitochondrial-Centric Perspective.International journal of molecular sciences · 2023Review
- Bcl-xL acts as an inhibitor of IPCell death and differentiation · 2022Article
- Allosteric cross-talk between the hydrophobic cleft and the BH4 domain of Bcl-2 in control of inositol 1,4,5-trisphosphate receptor activity.Exploration of targeted anti-tumor therapy · 2022Article
- The role of Bcl-2 proteins in modulating neuronal CaBiochimica et biophysica acta. Molecular cell research · 2021Review
- Bcl-2-Protein Family as Modulators of IPCold Spring Harbor perspectives in biology · 2020Review
- Partners in Crime: Towards New Ways of Targeting Calcium Channels.International journal of molecular sciences · 2019Review
- ABT-199 (Venetoclax), a BH3-mimetic Bcl-2 inhibitor, does not cause CaBritish journal of pharmacology · 2019Article
- Bcl-2 and IPCellular and molecular life sciences : CMLS · 2019Article
- Creating a New Cancer Therapeutic Agent by Targeting the Interaction between Bcl-2 and IPCold Spring Harbor perspectives in biology · 2019Review
- Constitutive IPCell death and differentiation · 2019Article
- Targeting Bcl-2-IPBiochimica et biophysica acta. Molecular cell research · 2018Review
- Emerging molecular mechanisms in chemotherapy: CaCell death & disease · 2018Review
- Subcellular Localization and Dynamics of the Bcl-2 Family of Proteins.Frontiers in cell and developmental biology · 2018Review
- Reciprocal sensitivity of diffuse large B-cell lymphoma cells to Bcl-2 inhibitors BIRD-2 versus venetoclax.Oncotarget · 2017Article
- Organelle membrane derived patches: reshaping classical methods for new targets.Scientific reports · 2017Article
- Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.The Journal of biological chemistry · 2017Article
- TMBIM-mediated CaBiochimica et biophysica acta. Molecular cell research · 2017Review
- Modulation of CaFrontiers in oncology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
The anti-apoptotic Bcl-2 protein is emerging as an efficient inhibitor of IP3R function, contributing to its oncogenic properties. Yet, the underlying molecular mechanisms remain not fully understood. Using mutations or pharmacological inhibition to antagonize Bcl-2's hydrophobic cleft, we excluded this functional domain as responsible for Bcl-2-mediated IP3Rs inhibition. In contrast, the deletion of the C-terminus, containing the trans-membrane domain, which is only present in Bcl-2α, but not in Bcl-2β, led to impaired inhibition of IP3R-mediated Ca2+ release and staurosporine-induced apoptosis. Strikingly, the trans-membrane domain was sufficient for IP3R binding and inhibition. We therefore propose a novel model, in which the Bcl-2's C-terminus serves as a functional anchor, which beyond mere ER-membrane targeting, underlies efficient IP3R inhibition by (i) positioning the BH4 domain in the close proximity of its binding site on IP3R, thus facilitating their interaction; (ii) inhibiting IP3R-channel openings through a direct interaction with the C-terminal region of the channel downstream of the channel-pore. Finally, since the hydrophobic cleft of Bcl-2 was not involved in IP3R suppression, our findings indicate that ABT-199 does not interfere with IP3R regulation by Bcl-2 and its mechanism of action as a cell-death therapeutic in cancer cells likely does not involve Ca2+ signaling.
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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.