ArticleProceedings of the National Academy of Sciences of the United States of America2008
Apoptosis is triggered when prosurvival Bcl-2 proteins cannot restrain Bax.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 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.
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Who cites it
105 citing papers in PubMed, 187 citations in OpenAlex.
- Deciphering Bax Dynamics: Regulation, Retrotranslocation, and Mitochondrial Interplay in the Commitment to Apoptosis: A Narrative Review.Health science reports · 2026Article
- A unified therapeutic theory for treating cancer via master regulators of the universal apoptosis network.Cell death discovery · 2026Review
- Effects of Polygonum cognatum Meissn. through modulation of hyperglycaemia, oxidative stress via Nrf-2/HO-1, apoptosis, NF-κB/TLR-4 pathways.Journal of molecular histology · 2026Article
- The BCL-2 protein family: from discovery to drug development.Cell death and differentiation · 2025Review
- Collaborative orchestration of BH3-only proteins governs Bak/Bax-dependent hepatocyte apoptosis under antiapoptotic protein-deficiency in mice.Cell death and differentiation · 2025Article
- Vitamin C Modulates the PI3K/AKT Pathway via Glutamate and Nitric Oxide in Developing Avian Retina Cells in Culture.Brain sciences · 2025Article
- Cell death in glioblastoma and the central nervous system.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- No Time to Die: How Cytomegaloviruses Suppress Apoptosis, Necroptosis, and Pyroptosis.Viruses · 2024Review
- Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.Acta pharmaceutica Sinica. B · 2024Review
- Diverse functions of cytochrome c in cell death and disease.Cell death and differentiation · 2024Review
- The function of alternative splicing in the proteome: rewiring protein interactomes to put old functions into new contexts.Nature structural & molecular biology · 2023Review
- The Role of Hydrogen Sulfide in the Localization and Expression of p53 and Cell Death in the Nervous Tissue in Traumatic Brain Injury and Axotomy.International journal of molecular sciences · 2023Article
- Activity-dependent regulation of the BAX/BCL-2 pathway protects cortical neurons from apoptotic death during early development.Cellular and molecular life sciences : CMLS · 2023Article
- CaMolecules and cells · 2023Article
- TREM2 inhibition triggers antitumor cell activity of myeloid cells in glioblastoma.Science advances · 2023Article
- Cold air plasma improving rheumatoid arthritis via mitochondrial apoptosis pathway.Bioengineering & translational medicine · 2023Article
- BCL-2-family protein tBID can act as a BAX-like effector of apoptosis.The EMBO journal · 2022Article
- NO-Dependent Mechanisms of p53 Expression and Cell Death in Rat's Dorsal Root Ganglia after Sciatic-Nerve Transection.Biomedicines · 2022Article
- Review
- Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A central issue in the control of apoptosis is whether its essential mediators Bax and Bak must be restrained by Bcl-2-like prosurvival relatives to prevent their damaging mitochondria and unleashing apoptosis. The issue is particularly vexed for Bax, which is largely a cytosolic monomer in unstressed cells. To determine whether Bax regulation requires its binding by prosurvival relatives, we replaced a conserved aspartate in its BH3 interaction domain with arginine. Bax D68R functioned and behaved like wild-type Bax in localization and activation but had greatly impaired binding to the prosurvival family members. Nevertheless, Bcl-x(L) remained able to block apoptosis induced by Bax D68R. Whereas cells with sufficient Bcl-x(L) tolerated expression of Bax D68R, it provoked apoptosis when Bcl-x(L) was absent, downregulated, or inactivated. Moreover, Bax D68R rendered membrane bound by a C-terminal anchor mutation overwhelmed endogenous Bcl-x(L) and killed cells. These unexpected results suggest that engagement of Bax by its prosurvival relatives is a major barrier to its full activation. We propose that the Bcl-2-like proteins must capture the small proportion of Bax molecules with an exposed BH3 domain, probably on the mitochondrial membrane, to prevent Bax-imposed cell death, but that Bcl-x(L) also controls Bax by other mechanisms.
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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.