ArticleCell cycle (Georgetown, Tex.)2010
p53 inactivation by MDM2 and MDMX negative feedback loops in testicular germ cell tumors.
Article in Cell cycle (Georgetown, Tex.), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 65 citations in OpenAlex.
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Male choriocarcinoma presenting with intracerebral hemorrhage: a case report and literature review.Frontiers in oncology · 2025Article
- A testis-specific lncRNA functions as a post-transcriptional regulator of MDM2 and stimulates apoptosis of testicular germ cell tumor cells.Cell death discovery · 2024Article
- Ganoderic Acid A and Its Amide Derivatives as Potential Anti-Cancer Agents by Regulating the p53-MDM2 Pathway: Synthesis and Biological Evaluation.Molecules (Basel, Switzerland) · 2023Article
- Genome-wide CRISPR/Cas9 screening for therapeutic targets in NSCLC carrying wild-type TP53 and receptor tyrosine kinase genes.Clinical and translational medicine · 2022Article
- Sempervirine inhibits RNA polymerase I transcription independently from p53 in tumor cells.Cell death discovery · 2020Article
- MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.The EMBO journal · 2020Article
- Cisplatin Resistance in Testicular Germ Cell Tumors: Current Challenges from Various Perspectives.Cancers · 2020Review
- α-Helix-Mimicking Sulfono-γ-AApeptide Inhibitors for p53-MDM2/MDMX Protein-Protein Interactions.Journal of medicinal chemistry · 2020Article
- Review
- Molecular Mechanisms of Cisplatin Chemoresistance and Its Circumventing in Testicular Germ Cell Tumors.Current oncology reports · 2018Review
- Optimal Affinity Enhancement by a Conserved Flexible Linker Controls p53 Mimicry in MdmX.Biophysical journal · 2017Article
- Negative auto-regulators trap p53 in their web.Journal of molecular cell biology · 2017Review
- Review
- MDM2 oligomers: antagonizers of the guardian of the genome.Oncogene · 2016Review
- Intra molecular interactions in the regulation of p53 pathway.Translational cancer research · 2016Article
- The genomic landscape of testicular germ cell tumours: from susceptibility to treatment.Nature reviews. Urology · 2016Review
- Autoinhibition of MDMX by intramolecular p53 mimicry.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The chemosensitivity of testicular germ cell tumors.Cellular oncology (Dordrecht, Netherlands) · 2014Review
- Negative regulation of p53 by Ras superfamily protein RBEL1A.Journal of cell science · 2013Article
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 2 institutions in 1 country.
Funding
Abstract
Testicular germ cell tumors (TGCT) are unique in their excellent response to DNA-damaging chemotherapy. Mutation of p53 is rare in both untreated and relapsed TGCTs, suggesting that p53 fails to respond effectively against malignant transformation in germ cells. Previous studies implicated the presence of a poorly defined TGCT-specific mechanism of p53 inactivation. Here we show that disruption of p53-MDM2 binding using the MDM2-specific inhibitor Nutlin activates p53 in TGCT cells and is sufficient to induce strong apoptosis. Knockdown of MDMX cooperates with Nutlin to activate p53. Surprisingly, we found that p53 activation induced a two-fold increase in MDMX mRNA and protein expression in TGCT cells. A p53-responsive promoter is identified in MDMX intron 1 that contains a functional p53-binding site, suggesting that MDMX also functions as a negative feedback regulator of p53 in a cell line-dependent fashion. These findings suggest that MDM2 and MDMX are responsible for the functional inactivation of p53 in TGCT. Furthermore, TGCT cells are unique in having a strong apoptosis response to p53. Direct activation of p53 by targeting MDM2 and MDMX may provide a backup approach for the treatment of TGCTs resistant to DNA-damaging drugs.
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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.