ArticleOncogene2005
Loss of p21 disrupts p14 ARF-induced G1 cell cycle arrest but augments p14 ARF-induced apoptosis in human carcinoma cells.
Article in Oncogene, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
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- Nucleolin loss of function leads to aberrant Fibroblast Growth Factor signaling and craniofacial anomalies.Development (Cambridge, England) · 2022Article
- Roles of ARF tumour suppressor protein in lung cancer: time to hit the nail on the head!Molecular and cellular biochemistry · 2021Review
- Defined factors to reactivate cell cycle activity in adult mouse cardiomyocytes.Scientific reports · 2019Article
- A simple model of a growing tumour.PeerJ · 2019Article
- CD44 variant-dependent redox status regulation in liver fluke-associated cholangiocarcinoma: A target for cholangiocarcinoma treatment.Cancer science · 2016Article
- Apoptosis resistance, mitotic catastrophe, and loss of ploidy control in Burkitt lymphoma.Journal of molecular medicine (Berlin, Germany) · 2015Article
- A Model for p38MAPK-Induced Astrocyte Senescence.PloS one · 2015Article
- Modelling the onset of senescence at the G1/S cell cycle checkpoint.BMC genomics · 2014Article
- 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
- 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
- Article
- p53-Responsive micrornas 192 and 215 are capable of inducing cell cycle arrest.Cancer research · 2008Article
- Cooperative effect of p21Cip1/WAF-1 and 14-3-3sigma on cell cycle arrest and apoptosis induction by p14ARF.Oncogene · 2008Article
- P21 and p27: roles in carcinogenesis and drug resistance.Expert reviews in molecular medicine · 2008Review
- Grape seed extract induces cell cycle arrest and apoptosis in human colon carcinoma cells.Nutrition and cancer · 2008Article
- Bak functionally complements for loss of Bax during p14ARF-induced mitochondrial apoptosis in human cancer cells.Oncogene · 2006Article
- Genetic dissection of apoptosis and cell cycle control in response of colorectal cancer treated with preoperative radiochemotherapy.BMC cancer · 2006Article
- Induction of p21CIP/WAF-1 and G2 arrest by ionizing irradiation impedes caspase-3-mediated apoptosis in human carcinoma cells.Oncogene · 2006Article
- In B-CLL, the codon 72 polymorphic variants of p53 are not related to drug resistance and disease prognosis.BMC cancer · 2005Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human INK4a locus encodes two structurally unrelated tumor suppressor proteins, p16 INK4a and p14 ARF (p19 ARF in the mouse), which are frequently inactivated in human cancer. Both the proapoptotic and cell cycle-regulatory functions of p14 ARF were initially proposed to be strictly dependent on a functional p53/mdm-2 tumor suppressor pathway. However, a number of recent reports have implicated p53-independent mechanisms in the regulation of cell cycle arrest and apoptosis induction by p14 ARF. Here, we show that the G1 cell cycle arrest induced by p14 ARF entirely depends on both p53 and p21 in human HCT116 and DU145 carcinoma cells. In contrast, neither loss of p53 nor p21 impaired apoptosis induction by p14 ARF as evidenced by nuclear DNA fragmentation, phosphatidyl serine exposure, and caspase activation, which included caspase-3/7- and caspase-9-like activities. However, lack of functional p21 resulted in the accumulation of cells in G2/M phase of the cell cycle and markedly enhanced p14 ARF-induced apoptosis that was, nevertheless, efficiently inhibited by the cell permeable broad-spectrum caspase inhibitor zVAD-fmk (valyl-alanyl-aspartyl-(O)-methyl)-fluoromethylketone). Thus, loss of cell cycle restriction point control in the absence of p21 may interfere with p14 ARF-induced apoptosis. Finally, these data indicate that the signaling events required for G1 cell cycle arrest and apoptosis induction by p14 ARF dissociate upstream of p53.
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