ArticleCellular signalling2020
Synergistic activation of p53 by actinomycin D and nutlin-3a is associated with the upregulation of crucial regulators and effectors of innate immunity.
Article in Cellular signalling, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 38 citations in OpenAlex.
- Differential STING and p53 expression in epidermodysplasia verruciformis-associated versus non-EV cutaneous squamous cell carcinomas.Medical oncology (Northwood, London, England) · 2026Article
- Review
- The 20-HETE/GPR75 Axis Drives NLRP1 Inflammasome Activation via p53 in Bronchopulmonary Dysplasia.Advanced biology · 2026Article
- From energy metabolic homeostasis to immune remodeling: the role and therapeutic potential of STING signaling in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Integrated single-cell and bulk RNA sequencing analysis identifies a pyroptosis related prognostic model for predicting prognosis and therapeutic response in intrahepatic cholangiocarcinoma.Discover oncology · 2026Article
- The p53 tumor suppressor modulates the expression of proteins that control natural killer cell activity.Cell communication and signaling : CCS · 2026Article
- p53-regulated non-apoptotic cell death pathways and their relevance in cancer and other diseases.Nature reviews. Molecular cell biology · 2025Review
- The puzzling regulation of the interferon signaling system by the p53 tumor suppressor protein.Cellular and molecular life sciences : CMLS · 2025Article
- Antibacterial Activity of the p53 Tumor Suppressor Protein-How Strong Is the Evidence?International journal of molecular sciences · 2025Review
- Comparison of Different Keratinocyte Cell Line Models for Analysis of NLRP1 Inflammasome Activation.Biomolecules · 2024Article
- Inverse correlation between TP53 gene status and PD-L1 protein levels in a melanoma cell model depends on an IRF1/SOX10 regulatory axis.Cellular & molecular biology letters · 2024Article
- The Strong Activation of p53 Tumor Suppressor Drives the Synthesis of the Enigmatic Isoform of DUSP13 Protein.Biomedicines · 2024Article
- Review
- At the Crossroads of the cGAS-cGAMP-STING Pathway and the DNA Damage Response: Implications for Cancer Progression and Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate.Cell research · 2023Article
- The Wheel of p53 Helps to Drive the Immune System.International journal of molecular sciences · 2023Review
- The role of p53 in anti-tumor immunity and response to immunotherapy.Frontiers in molecular biosciences · 2023Review
- Benzo[Frontiers in immunology · 2023Article
- Review
- Transcriptome Analysis of Cells Exposed to Actinomycin D and Nutlin-3a Reveals New Candidate p53-Target Genes and Indicates That CHIR-98014 Is an Important Inhibitor of p53 Activity.International journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Actinomycin D and nutlin-3a (A + N) activate p53, partly through induction of phosphorylation on Ser392. The death of A549 cells induced by A + N morphologically resembles inflammation-inducing pyroptosis - cell destruction triggered by activated caspase-1. The treatment with A + N (or camptothecin) strongly upregulated caspase-1 and its two activators: IFI16 and NLRP1, however, caspase-1 activation was not detected. A549 cells may have been primed for pyroptosis, with the absence of a crucial trigger. The investigation of additional innate immunity elements revealed that A + N (or camptothecin) stimulated the expression of NLRX1, STING (stimulator of interferon genes) and two antiviral proteins, IFIT1 and IFIT3. IFI16 and caspase-1 are coded by p53-regulated genes which led us to investigate regulation of NLRP1, NLRX1, STING, IFIT1 and IFIT3 in p53-dependent mode. The upregulation of NLRP1, NLRX1 and STING was attenuated in p53 knockdown cells. The upsurge of the examined genes, and activation of p53, was inhibited by C16, an inhibitor of PKR kinase. PKR was tested due to its ability to phosphorylate p53 on Ser392. Surprisingly, C16 was active even in PKR knockdown cells. The ability of C16 to prevent activation of p53 and expression of innate immunity genes may be the source of its strong anti-inflammatory action. Moreover, cells exposed to A + N can influence neighboring cells in paracrine fashion, for instance, they shed ectodomain of COL17A1 protein and induce, in p53-dependent mode, the expression of gene for interleukin-7. Further, the activation of p53 also spurred the expression of SOCS1, an inhibitor of interferon triggered STAT1-dependent signaling. We conclude that, stimulation of p53 primes cells for the production of interferons (through upregulation of STING), and may activate negative-feedback within this signaling system by enhancing the production of SOCS1.
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.