ArticleCell death & disease2016
Bax/Bak activation in the absence of Bid, Bim, Puma, and p53.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- Review
- Article
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- To be or not to be: navigating the influence of MicroRNAs on cervical cancer cell death.Cancer cell international · 2025Review
- Anti-Cancer Bioactive Peptide Induces Apoptosis in Gastric Cancer Cells through TP53 Signaling Cascade.Protein and peptide letters · 2025Article
- Notopterygium Incisum Extract Promotes Apoptosis by Preventing the Degradation of BIM in Colorectal Cancer.Current medical science · 2024Article
- The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.The Biochemical journal · 2024Review
- Central role of podocytes in mediating cellular cross talk in glomerular health and disease.American journal of physiology. Renal physiology · 2024Review
- Iodine-Biofortified Lettuce Can Promote Mitochondrial Dependent Pathway of Apoptosis in Human Gastrointestinal Cancer Cells.International journal of molecular sciences · 2023Article
- Human papillomavirus infection, cervical cancer and the less explored role of trace elements.Biological trace element research · 2023Review
- Cytotoxic and Apoptotic Effects of Chemogenic and Biogenic Nano-sulfur on Human Carcinoma Cells: A Comparative Study.ACS omega · 2021Article
- Titania Nanosheet Generates Peroxynitrite-DependentPharmaceutics · 2021Article
- Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death.Oncotarget · 2021Article
- Review
- Review
- Huanglian decoction suppresses the growth of hepatocellular carcinoma cells by reducingWorld journal of gastroenterology · 2021Article
- Changes in Apoptotic Pathways in MOLM-13 Cell Lines after Induction of Resistance to Hypomethylating Agents.International journal of molecular sciences · 2021Article
- Apoptosis and Cell Proliferation Markers in Inflammatory-Fibroproliferative Diseases of the Vessel Wall (Review).Sovremennye tekhnologii v meditsine · 2021Review
- Chronic and Acute Toxicities of Aflatoxins: Mechanisms of Action.International journal of environmental research and public health · 2020Review
- Apoptotic cell-derived exosomes: messages from dying cells.Experimental & molecular medicine · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
How BH3-only proteins activate Bax/Bak, the two gateway proteins of the mitochondria-dependent apoptotic pathway, remains incompletely understood. Although all pro-apoptotic BH3-only proteins are known to bind/neutralize the anti-apoptotic Bcl-2 proteins, the three most potent ones, Bid (tBid), Bim, and Puma, possess an additional activity of directly activating Bax/Bak in vitro. This latter activity has been proposed to be responsible for triggering Bax/Bak activation following apoptotic stimulation. To test this hypothesis, we generated Bid(-/)(-)Bim(-/)(-)Puma(-/)(-) (TKO), TKO/Bax(-/)(-)/Bak(-/)(-) (PentaKO), and PentaKO/Mcl-1(-/-) (HexaKO) HCT116 cells through gene editing. Surprisingly, although the TKO cells were resistant to several apoptotic stimuli, robust apoptosis was induced upon the simultaneous inactivation of Bcl-xL and Mcl-1, two anti-apoptotic Bcl-2 proteins known to suppress Bax/Bak activation and activity. Importantly, such apoptotic activity was completely abolished in the PentaKO cells. In addition, ABT-737, a BH3 mimetic that inhibits Bcl-xL/Bcl-w/Bcl-2, induced Bax activation in HexaKO cells reconstituted with endogenous level of GFP-Bax. Further, by generating TKO/p53(-/-) (QKO) cells, we demonstrated that p53, a tumor suppressor postulated to directly activate Bax, is not required for Bid/Bim/Puma-independent Bax/Bak activation. Together, these results strongly suggest that the direct activation activities of Bid (tBid), Bim, Puma, and p53 are not essential for activating Bax/Bak once the anti-apoptotic Bcl-2 proteins are neutralized.
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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.