ArticleOncogene2002
Adenovirus-mediated overexpression of p14(ARF) induces p53 and Bax-independent apoptosis.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 109 citations in OpenAlex.
- Expression of the c-myc gene as a predictor of chemotherapy response and a prognostic factor in patients with ovarian cancer.Cancer science · 2004Trial
- Genetic Medicine Approaches for Tumor Suppressor Loss: Therapeutic Replacement with Self-Amplifying RNA.Pharmaceutical research · 2026Review
- The cell cycle regulator p16 promotes tumor infiltrated CD8Cell death & disease · 2024Article
- Synthesis and in vitro Activity of Eugenyl Benzoate Derivatives as BCL-2 Inhibitor in Colorectal Cancer with QSAR and Molecular Docking Approach.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Taxanes Sensitize Prostate Cancer Cells to TRAIL-Induced Apoptotic Synergy via Endoplasmic Reticulum Stress.Molecular cancer therapeutics · 2021Article
- Roles of ARF tumour suppressor protein in lung cancer: time to hit the nail on the head!Molecular and cellular biochemistry · 2021Review
- Fusaric Acid immunotoxicity and MAPK activation in normal peripheral blood mononuclear cells and Thp-1 cells.Scientific reports · 2017Article
- Nonpromoter methylation of the CDKN2A gene with active transcription is associated with improved locoregional control in laryngeal squamous cell carcinoma.Cancer medicine · 2017Article
- All-trans retinoic acid and genistein induce cell apoptosis in OVCAR-3 cells by increasing the P14 tumor suppressor gene.Research in pharmaceutical sciences · 2016Article
- Dynamics of ARF regulation that control senescence and cancer.BMB reports · 2016Review
- Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells.Molecular cancer therapeutics · 2014Article
- A genotoxic stress-responsive miRNA, miR-574-3p, delays cell growth by suppressing the enhancer of rudimentary homolog gene in vitro.International journal of molecular sciences · 2014Article
- Modelling the onset of senescence at the G1/S cell cycle checkpoint.BMC genomics · 2014Article
- Siva1 inhibits p53 function by acting as an ARF E3 ubiquitin ligase.Nature communications · 2013Article
- Bak is a key molecule in apoptosis induced by methanol extracts of Codonopsis lanceolata and Tricholoma matsutake in HSC-2 human oral cancer cells.Oncology letters · 2012Article
- 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
- Potent growth-inhibitory effect of TRAIL therapy mediated by double-regulated oncolytic adenovirus on osteosarcoma.Molecular and cellular biochemistry · 2012Article
- P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the expression of TIMP3.The Journal of clinical investigation · 2012Article
- MicroRNA-149 inhibits proliferation and cell cycle progression through the targeting of ZBTB2 in human gastric cancer.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human INK4a gene locus encodes two structurally unrelated tumor suppressor proteins, p16(INK4a) and p14(ARF), which are frequently inactivated in human cancer. Whereas p16(INK4a) acts through engagement of the Rb-cdk4/6-cyclin D pathway, both the pro-apoptotic and cell cycle-regulatory functions of p14(ARF) were shown to be primarily dependent on the presence of functional p53. Recent reports have also implicated p14(ARF) in p53-independent mechanisms of cell cycle regulation and apoptosis induction, respectively. To further explore the pro-apoptotic function of p14(ARF) in relation to functional cellular p53, we constructed a replication-deficient adenoviral vector for overexpression of p14(ARF) (Ad-p14(ARF)). As expected, Ad-p14(ARF) efficiently induced apoptosis in p53/Rb wild-type U-2OS osteosarcoma cells at low multiplicities of infection. Interestingly, Ad-p14(ARF) also induced apoptosis in both p53-deleted SAOS-2 osteosarcoma cells and HCT116 colon cancer cells with a bi-allelic knock-out of p53 (HCT116-p53(-/-)). Similarly, adenovirus-mediated overexpression of p14(ARF) induced apoptosis in p53/Bax-mutated DU145 prostate cancer cells as well as in HCT116 cells devoid of functional Bax (HCT116-Bax(-/-)). Restoration of Bax expression by retroviral gene transfer in DU145 cells did not further enhance p14(ARF)-triggered cell death. Infection with Ad-p14(ARF) induced activation of mitochondrial permeability shift transition, caspase activation and apoptotic DNA fragmentation irrespective of the presence or absence of either Bax or functional cellular p53. Nevertheless, overexpression of the anti-apoptotic Bcl-2 homolog Bcl-x(L) markedly inhibited p14(ARF)-induced apoptosis. This may indicate that p14(ARF) triggers a so far unknown activator of mitochondrial apoptosis which can be inhibited by Bcl-2 but which acts either independently or downstream of Bax. Taken together, this report demonstrates the participation of signaling pathways apart from the p53/Mdm-2 rheostat and Bax in p14(ARF)-mediated apoptosis.
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