ArticleCell death and differentiation2015
A unique role for p53 in the regulation of M2 macrophage polarization.
Article in Cell death and differentiation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 164 citations in OpenAlex.
- Lipid Nanoparticle Co-Delivery of mRNA and a Small Molecule Drug for Oral Cancer Chemoimmunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Disruption of macrophage migration inhibitory factor signaling induces major tumor-associated macrophage phenotypes in human M2 macrophages.Molecular biomedicine · 2026Article
- Aging and cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Pro- and Anti-Inflammatory Macrophages Adjust UCP2 Protein Levels Based on Their Intrinsic Metabolism and Available Metabolites.European journal of immunology · 2026Article
- Syringin disrupts the DLAT/MYC axis to dampen TAM polarization and suppress hepatocellular carcinoma progression.Acta pharmaceutica Sinica. B · 2026Article
- Homeobox A10 in gastrointestinal malignancies: unraveling metastatic mechanisms and novel therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Integrated analyses reveal a potential role for PFKFB4 in M2 macrophage polarization and hepatocellular carcinoma progression.Cancer cell international · 2026Article
- Elevated lactate in AML bone marrow contributes to macrophage polarization via GPR81 signaling.Blood advances · 2026Article
- Is ER-positive breast cancer a shield against myocardial infarction and its complications? A Mendelian randomization approach.BMC cardiovascular disorders · 2026Article
- A novel β-carboline alkaloid derivative targeting MDM2-p53 pathway suppresses colorectal cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Regulation of macrophage transcriptional dynamics during acute and chronic wound repair.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Inhalability and Bioactivity of Spray-Dried versus Pressurized Gas eXpanded Liquid Technology-Processed Yeast Beta-Glucan Microparticles for Anti-Fibrotic Therapies.Advanced healthcare materials · 2025Article
- Lipid nanoparticle co-delivery of mRNA and a small molecule drug for oral cancer chemoimmunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Dissecting cross-lineage tumourigenesis under p53 inactivation through single-cell multi-omics and spatial transcriptomics.Clinical and translational medicine · 2025Article
- ISCU-p53 axis orchestrates macrophage polarization to dictate immunotherapy response in esophageal squamous cell carcinoma.Cell death & disease · 2025Article
- Tumor microenvironment noise-induced polarization: the main challenge in macrophages' immunotherapy for cancer.Molecular and cellular biochemistry · 2025Review
- Review
- C1QMolecular cancer · 2025Article
- Elevated Lactate in the AML Bone Marrow Microenvironment Polarizes Leukemia-Associated Macrophages via GPR81 Signaling.bioRxiv : the preprint server for biology · 2025Article
- Myeloid Mir34a suppresses colitis-associated colon cancer: characterization of mediators by single-cell RNA sequencing.Cell death and differentiation · 2025Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P53 is critically important in preventing oncogenesis but its role in inflammation in general and in the function of inflammatory macrophages in particular is not clear. Here, we show that bone marrow-derived macrophages exhibit endogenous p53 activity, which is increased when macrophages are polarized to the M2 (alternatively activated macrophage) subtype. This leads to reduced expression of M2 genes. Nutlin-3a, which destabilizes the p53/MDM2 (mouse double minute 2 homolog) complex, promotes p53 activation and further downregulates M2 gene expression. In contrast, increased expression of M2 genes was apparent in M2-polarized macrophages from p53-deficient and p53 mutant mice. Furthermore, we show, in mice, that p53 also regulates M2 polarization in peritoneal macrophages from interleukin-4-challenged animals and that nutlin-3a retards the development of tolerance to Escherichia coli lipopolysaccharide. P53 acts via transcriptional repression of expression of c-Myc (v-myc avian myelocytomatosis viral oncogene homolog) gene by directly associating with its promoter. These data establish a role for the p53/MDM2/c-MYC axis as a physiological 'brake' to the M2 polarization process. This work reveals a hitherto unknown role for p53 in macrophages, provides further insight into the complexities of macrophage plasticity and raises the possibility that p53-activating drugs, many of which are currently being trialled clinically, may have unforeseen effects on macrophage function.
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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.