ArticleOncogene2006
Bak functionally complements for loss of Bax during p14ARF-induced mitochondrial apoptosis in human cancer cells.
Article in Oncogene, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 45 citations in OpenAlex.
- BAK knockdown delays bleaching and alleviates oxidative DNA damage in a reef-building coral.Communications biology · 2025Article
- Anticancer activity of MDM2 inhibition in 2D and bioprinted 3D retinoblastoma cell models.Frontiers in pharmacology · 2025Article
- Roles of ARF tumour suppressor protein in lung cancer: time to hit the nail on the head!Molecular and cellular biochemistry · 2021Review
- Article
- Caspase-3 feedback loop enhances Bid-induced AIF/endoG and Bak activation in Bax and p53-independent manner.Cell death & disease · 2015Article
- Mitochondrial p53 phosphorylation induces Bak-mediated and caspase-independent cell death.Oncotarget · 2015Article
- Article
- p14(ARF)-induced apoptosis in p53 protein-deficient cells is mediated by BH3-only protein-independent derepression of Bak protein through down-regulation of Mcl-1 and Bcl-xL proteins.The Journal of biological chemistry · 2012Article
- Targeting colorectal cancer stem cells with inducible caspase-9.Apoptosis : an international journal on programmed cell death · 2012Article
- Apoptosis induced by knockdown of uPAR and MMP-9 is mediated by inactivation of EGFR/STAT3 signaling in medulloblastoma.PloS one · 2012Article
- Differential regulation of the proapoptotic multidomain protein Bak by p53 and p73 at the promoter level.Cell death and differentiation · 2011Article
- Systematic genetic dissection of p14ARF-mediated mitochondrial cell death signaling reveals a key role for p21CDKN1 and the BH3-only protein Puma/bbc3.Journal of molecular medicine (Berlin, Germany) · 2010Article
- Endogenous Bak inhibitors Mcl-1 and Bcl-xL: differential impact on TRAIL resistance in Bax-deficient carcinoma.The Journal of cell biology · 2010Article
- Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF.Oncogene · 2008Article
- Dynamin-2-dependent targeting of mannheimia haemolytica leukotoxin to mitochondrial cyclophilin D in bovine lymphoblastoid cells.Infection and immunity · 2008Article
- Mitochondrial p32 is a critical mediator of ARF-induced apoptosis.Cancer cell · 2008Article
- Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis.The Journal of cell biology · 2007Article
- Cisplatin Activates the Growth Inhibitory Signaling Pathways by Enhancing the Production of Reactive Oxygen Species in Non-small Cell Lung Cancer Carrying an EGFR Exon 19 Deletion.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
In contrast to the initial notion that the biological activity of p14(ARF) strictly depends on a functional mdm-2/p53 signaling axis, we recently demonstrated that p14(ARF) mediates apoptosis in a p53/Bax-independent manner. Here, we show that p14(ARF) induces breakdown of the mitochondrial membrane potential and cytochrome c release before triggering caspase-9- and caspase-3/7-like activities in p53/Bax-deficient DU145 prostate cancer cells expressing wild-type Bak. Re-expression of Bax in these cells failed to further enhance p14(ARF)-induced apoptosis, suggesting that p14(ARF)-induced apoptosis primarily depends on Bak but not Bax in these cells. To further define the role of Bak and Bax in p14(ARF)-induced mitochondrial apoptosis, we employed short interference RNA for the knockdown of bak in isogeneic, p53 wild-type HCT116 colon cancer cells either proficient or deficient for Bax. There, combined loss of Bax and Bak attenuated p14(ARF)-induced apoptosis whereas single loss of Bax or Bak was only marginally effective, as in the case of DU145. Notably, HCT116 cells deficient for Bax and Bak failed to release cytochrome c and showed attenuated activation of caspase-9 (LEHDase) and caspase-3/caspase-7 (DEVDase) upon p14(ARF) expression. These data indicate that p14(ARF) triggers apoptosis via a Bax/Bak-dependent pathway in p53-proficient HCT116, whereas Bax is dispensable in p53-deficient DU145 cells. Nevertheless, a substantial proportion of p14(ARF)-induced cell death proceeds in a Bax/Bak-independent manner. This is also the case for inhibition of clonogenic growth that occurs, at least in part, through an entirely Bax/Bak-independent mechanism.
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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.