ArticleGenes & cancer2011
Activation of p21-Dependent G1/G2 Arrest in the Absence of DNA Damage as an Antiapoptotic Response to Metabolic Stress.
Article in Genes & cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
45 citing papers in PubMed, 56 citations in OpenAlex.
- p53 and p21 Status Influences Cellular Response to Metformin inCurrent issues in molecular biology · 2026Article
- Clinical implications of 10-formyltetrahydrofolate dehydrogenase expression in hormone receptor-positive breast cancer.Frontiers in oncology · 2026Article
- Differential Expression of One-Carbon Pathway Enzyme ALDH1L1 Is Linked to Tumorigenicity of Low-Grade Bladder Cancer Cells Through Metabolic Reprogramming.Cancer medicine · 2025Article
- Endothelial Effects in the Elderly: Fibroblast Regulation in Soft Tissue Healing.Journal of cellular physiology · 2025Article
- The hydroxamate based HDAC inhibitor WMJ-J-09 induces colorectal cancer cell death by targeting tubulin and downregulating survivin.Scientific reports · 2025Article
- Article
- PYGO2 promotes resistance to chemotherapy via reducing apoptosis and G2/M cell cycle arrest in esophageal carcinoma cells.Medical oncology (Northwood, London, England) · 2025Article
- Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance in Cancer Cells.Current gene therapy · 2025Review
- Transcriptome analysis of the effects of high temperature on zygotic genome activation in porcine embryos.Scientific reports · 2024Article
- Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.Cancer & metabolism · 2024Article
- Article
- Studying Hepatic Stellate Cell Senescence.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Exploratory Metabolomics Underscores the Folate Enzyme ALDH1L1 as a Regulator of Glycine and Methylation Reactions.Molecules (Basel, Switzerland) · 2022Article
- In vitro generation of transplantable insulin-producing cells from canine adipose-derived mesenchymal stem cells.Scientific reports · 2022Article
- Aldehyde Dehydrogenase 2 as a Therapeutic Target in Oxidative Stress-Related Diseases: Post-Translational Modifications Deserve More Attention.International journal of molecular sciences · 2022Review
- Ubiquitin-specific protease 3 attenuates interleukin-1β-mediated chondrocyte senescence by deacetylating forkhead box O-3 via sirtuin-3.Bioengineered · 2022Article
- Structure of putative tumor suppressor ALDH1L1.Communications biology · 2022Article
- Article
- Aldh1l2 knockout mouse metabolomics links the loss of the mitochondrial folate enzyme to deregulation of a lipid metabolism observed in rare human disorder.Human genomics · 2020Article
- Folate pathways mediating the effects of ethanol in tumorigenesis.Chemico-biological interactions · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The folate enzyme, FDH (10-formyltetrahydrofolate dehydrogenase, ALDH1L1), a metabolic regulator of proliferation, activates p53-dependent G1 arrest and apoptosis in A549 cells. In the present study, we have demonstrated that FDH-induced apoptosis is abrogated upon siRNA knockdown of the p53 downstream target PUMA. Conversely, siRNA knockdown of p21 eliminated FDH-dependent G1 arrest and resulted in an early apoptosis onset. The acceleration of FDH-dependent apoptosis was even more profound in another cell line, HCT116, in which the p21 gene was silenced through homologous recombination (p21(-/-) cells). In contrast to A549 cells, FDH caused G2 instead of G1 arrest in HCT116 p21(+/+) cells; such an arrest was not seen in p21-deficient (HCT116 p21(-/-)) cells. In agreement with the cell cycle regulatory function of p21, its strong accumulation in nuclei was seen upon FDH expression. Interestingly, our study did not reveal DNA damage upon FDH elevation in either cell line, as judged by comet assay and the evaluation of histone H2AX phosphorylation. In both A549 and HCT116 cell lines, FDH induced a strong decrease in the intracellular ATP pool (2-fold and 30-fold, respectively), an indication of a decrease in de novo purine biosynthesis as we previously reported. The underlying mechanism for the drop in ATP was the strong decrease in intracellular 10-formyltetrahydrofolate, a substrate in two reactions of the de novo purine pathway. Overall, we have demonstrated that p21 can activate G1 or G2 arrest in the absence of DNA damage as a response to metabolite deprivation. In the case of FDH-related metabolic alterations, this response delays apoptosis but is not sufficient to prevent cell death.
Indexed as
Identifiers
What OpenQuestion holds
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.