ArticleCellular & molecular biology letters2020
The MDM2 ligand Nutlin-3 differentially alters expression of the immune blockade receptors PD-L1 and CD276.
Article in Cellular & molecular biology letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Cell Penetrating Thyclotides Facilitate Efficient Delivery of Bioactive Peptides into Cells.bioRxiv : the preprint server for biology · 2026Article
- Insight of immune checkpoint blockades in melanoma: mechanism and clinical translation.Molecular cancer · 2026Review
- Helicobacter pylori Lipopolysaccharide Upregulates MDM2 via the TLR4/MAPK/AP-1 Pathway to Promote Gastric Cancer Progression.Digestive diseases and sciences · 2026Article
- Article
- A strategy for synergistic enhancement of immune circulation in head and neck squamous cell carcinoma by novel nucleic acid drug therapy and immunotherapy.Journal of translational medicine · 2025Review
- Unveiling the nexus of p53 and PD-L1: insights into immunotherapy resistance mechanisms in hepatocellular carcinoma.American journal of cancer research · 2025Review
- Article
- MDM2 inhibitors in cancer immunotherapy: Current status and perspective.Genes & diseases · 2024Review
- 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
- AC099850.3 promotes HBV-HCC cell proliferation and invasion through regulating CD276: a novel strategy for sorafenib and immune checkpoint combination therapy.Journal of translational medicine · 2024Article
- MDM2: current research status and prospects of tumor treatment.Cancer cell international · 2024Review
- MDM2 Inhibitors for Cancer Therapy: The Past, Present, and Future.Pharmacological reviews · 2024Review
- Metabolite itaconate in host immunoregulation and defense.Cellular & molecular biology letters · 2023Review
- The role of E3 ubiquitin ligases and deubiquitinases in bladder cancer development and immunotherapy.Frontiers in immunology · 2023Review
- Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment.Nature reviews. Drug discovery · 2022Review
- CRISPR/Cas9 application in cancer therapy: a pioneering genome editing tool.Cellular & molecular biology letters · 2022Review
- Resistance mechanisms to inhibitors of p53-MDM2 interactions in cancer therapy: can we overcome them?Cellular & molecular biology letters · 2021Review
- An integrated DNA and RNA variant detector identifies a highly conserved three base exon in theRNA biology · 2021Article
- Pharmacologic Activation of p53 Triggers Viral Mimicry Response Thereby Abolishing Tumor Immune Evasion and Promoting Antitumor Immunity.Cancer discovery · 2021Article
- Depleting Tumor Cells Expressing Immune Checkpoint Ligands-A New Approach to Combat Cancer.Cells · 2021Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
backgroundThe links between the p53/MDM2 pathway and the expression of pro-oncogenic immune inhibitory receptors in tumor cells are undefined. In this report, we evaluate whether there is p53 and/or MDM2 dependence in the expression of two key immune receptors, CD276 and PD-L1.
methodsProximity ligation assays were used to quantify protein-protein interactions in situ in response to Nutlin-3. A panel of p53-null melanoma cells was created using CRISPR-Cas9 guide RNA mediated genetic ablation. Flow cytometric analyses were used to assess the impact of
resultsCD276 forms protein-protein interactions with MDM2 in response to Nutlin-3, similar to the known MDM2 interactors p53 and HSP70. Isogenic HCT116 p53-wt/null cancer cells demonstrated that CD276 is induced on the cell surface by Nutlin-3 in a p53-dependent manner. PD-L1 was also unexpectedly induced by Nutlin-3, but PD-L1 does not bind MDM2. The ATM inhibitor KU55993 reduced the levels of PD-L1 under conditions where Nutlin-3 induces PD-L1, indicating that MDM2 and ATM have opposing effects on PD-L1 steady-state levels. PD-L1 is also up-regulated in response to genetic ablation of
conclusionGenetic inactivation of
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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.