ArticleGenes & development2016
Physiological restraint of Bak by Bcl-xL is essential for cell survival.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 47 citations in OpenAlex.
- Direct binding of the C-terminal sequences of Bim and Bak contributes to efficient Bak activation.Cell death and differentiation · 2026Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- Mitoquinone Can Effectively Improve the Quality of Thawed Boar Sperm.Animals : an open access journal from MDPI · 2025Article
- Deciphering molecular specificity in MCL-1/BAK interaction and its implications for designing potent MCL-1 inhibitors.Cell death and differentiation · 2025Article
- Inhibition of BAK-mediated apoptosis by the BH3-only protein BNIP5.Cell death and differentiation · 2025Article
- BECLIN-1 is essential for the maintenance of gastrointestinal epithelial integrity by regulating endocytic trafficking, F-actin organization, and lysosomal function.Autophagy reports · 2025Article
- The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.The Biochemical journal · 2024Review
- Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.PLoS biology · 2023Article
- BCLXL PROTAC degrader DT2216 targets secondary plasma cell leukemia addicted to BCLXL for survival.Frontiers in oncology · 2023Article
- Overcoming apoptotic resistance afforded by Bcl-2 in lymphoid tumor cells: a critical role for dexamethasone.Cell death discovery · 2022Article
- Decoding the concealed transcriptional signature of the apoptosis-related BCL2 antagonist/killer 1 (BAK1) gene in human malignancies.Apoptosis : an international journal on programmed cell death · 2022Article
- Advances in the pharmacological management of acute myeloid leukemia in adults.Expert opinion on pharmacotherapy · 2022Article
- Physiological and pharmacological modulation of BAX.Trends in pharmacological sciences · 2022Review
- Article
- Dynamic reconfiguration of pro-apoptotic BAK on membranes.The EMBO journal · 2021Article
- Robust autoactivation for apoptosis by BAK but not BAX highlights BAK as an important therapeutic target.Cell death & disease · 2020Article
- Germline heterozygous mutations in Nxf1 perturb RNA metabolism and trigger thrombocytopenia and lymphopenia in mice.Blood advances · 2020Article
- Venetoclax for AML: changing the treatment paradigm.Blood advances · 2019Article
- The Structural Biology of Bcl-xInternational journal of molecular sciences · 2019Review
- Pharmacological targeting of HSP90 with 17-AAG induces apoptosis of myogenic cells through activation of the intrinsic pathway.Molecular and cellular biochemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Due to the myriad interactions between prosurvival and proapoptotic members of the Bcl-2 family of proteins, establishing the mechanisms that regulate the intrinsic apoptotic pathway has proven challenging. Mechanistic insights have primarily been gleaned from in vitro studies because genetic approaches in mammals that produce unambiguous data are difficult to design. Here we describe a mutation in mouse and human Bak that specifically disrupts its interaction with the prosurvival protein Bcl-xL Substitution of Glu75 in mBak (hBAK Q77) for leucine does not affect the three-dimensional structure of Bak or killing activity but reduces its affinity for Bcl-xL via loss of a single hydrogen bond. Using this mutant, we investigated the requirement for physical restraint of Bak by Bcl-xL in apoptotic regulation. In vitro, Bak(Q75L) cells were significantly more sensitive to various apoptotic stimuli. In vivo, loss of Bcl-xL binding to Bak led to significant defects in T-cell and blood platelet survival. Thus, we provide the first definitive in vivo evidence that prosurvival proteins maintain cellular viability by interacting with and inhibiting Bak.
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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.