ArticleProceedings of the National Academy of Sciences of the United States of America2006
Macrophage inhibitory cytokine 1 mediates a p53-dependent protective arrest in S phase in response to starvation for DNA precursors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 62 citations in OpenAlex.
- Potential Markers to Differentiate Uterine Leiomyosarcomas from Leiomyomas.International journal of medical sciences · 2024Review
- Urinary Growth Differentiation Factor-15 (GDF15) levels as a biomarker of adverse outcomes and biopsy findings in chronic kidney disease.Journal of nephrology · 2021Article
- Renoprotective and Immunomodulatory Effects of GDF15 following AKI Invoked by Ischemia-Reperfusion Injury.Journal of the American Society of Nephrology : JASN · 2020Article
- Growth Differentiation Factor-15-Induced Contractile Activity and Extracellular Matrix Production in Human Trabecular Meshwork Cells.Investigative ophthalmology & visual science · 2016Article
- Acquisition of Chemoresistance and Other Malignancy-related Features of Colorectal Cancer Cells Are Incremented by Ribosome-inactivating Stress.The Journal of biological chemistry · 2016Article
- Role of GDF15 (growth and differentiation factor 15) in pulmonary oxygen toxicity.Toxicology in vitro : an international journal published in association with BIBRA · 2015Article
- Article
- The Role of Dihydroorotate Dehydrogenase in Apoptosis Induction in Response to Inhibition of the Mitochondrial Respiratory Chain Complex III.Acta naturae · 2014Article
- Article
- Genistein induces G2/M cell cycle arrest and apoptosis via ATM/p53-dependent pathway in human colon cancer cells.International journal of oncology · 2013Article
- Prolonged NF-κB activation by a macrophage inhibitory cytokine 1-linked signal in enteropathogenic Escherichia coli-infected epithelial cells.Infection and immunity · 2013Article
- N-(phosphonacetyl)-L-aspartate induces TAp73-dependent apoptosis by modulating multiple Bcl-2 proteins: potential for cancer therapy.Oncogene · 2013Article
- Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions.International journal of molecular sciences · 2013Article
- PRAP1 is a novel executor of p53-dependent mechanisms in cell survival after DNA damage.Cell death & disease · 2012Article
- Conserved Peptide Upstream Open Reading Frames are Associated with Regulatory Genes in Angiosperms.Frontiers in plant science · 2012Article
- Inhibitory member of the apoptosis-stimulating protein of p53 (ASPP) family promotes growth and tumorigenesis in human p53-deficient prostate cancer cells.Prostate cancer and prostatic diseases · 2011Article
- p53-Dependent p21-mediated growth arrest pre-empts and protects HCT116 cells from PUMA-mediated apoptosis induced by EGCG.Cancer letters · 2010Article
- Pyrimidine biosynthesis links mitochondrial respiration to the p53 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Glutamine deprivation induces abortive s-phase rescued by deoxyribonucleotides in k-ras transformed fibroblasts.PloS one · 2009Article
- Implication of human N-alpha-acetyltransferase 5 in cellular proliferation and carcinogenesis.Oncogene · 2008Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
p53 is essential for the cellular responses to DNA damage that help to maintain genomic stability. Protective p53-dependent cell-cycle checkpoints are activated in response to a wide variety of stresses, including not only DNA damage but also arrest of DNA synthesis and of mitosis. In addition to its role in activating the G(1) and G(2) checkpoints, p53 also helps to protect cells in S phase when they are starved for DNA precursors by treatment with the specific aspartate transcarbamylase inhibitor N-phosphonacetyl-l-aspartate (PALA), which blocks the synthesis of pyrimidine nucleotides. Even though p53 is activated, PALA-treated cells expressing low levels of p53 or lacking expression of p21 do not arrest in G(1) or G(2) but are blocked in S phase instead. In the complete absence of p53, PALA-treated cells continue to synthesize DNA slowly and eventually progress through S phase, suffering severe DNA damage that in turn triggers apoptosis. Expression of the secreted protein macrophage inhibitory cytokine 1 (MIC-1), a member of the TGF-beta superfamily, increases substantially after PALA treatment, and application of exogenous MIC-1 or its constitutive expression from a cDNA provides remarkable protection of p53-null cells from PALA-mediated apoptosis, arguing that the p53-dependent secretion of MIC-1 provides a major part of such protection. Stimulation of MIC-1-dependent S phase arrest in normal gut epithelial cells might help to revitalize the clinical use of PALA, which has been limited by gut toxicity.
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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.