ArticleProceedings of the National Academy of Sciences of the United States of America2005
The p53 regulatory gene MDM2 is a direct transcriptional target of MYCN in neuroblastoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.
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Who cites it
130 citing papers in PubMed, 228 citations in OpenAlex.
- Idasanutlin in Combination with Chemotherapy or Venetoclax in Pediatric and Young Adult Patients with Relapsed/Refractory Solid Tumors (iMATRIX Idasa): Results of a Phase I/II, Multicenter, Multi-arm Study.Targeted oncology · 2026Trial
- Role of the MDM2/p53 axis in regulating cisplatin response in tumor cells.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Piwil-2 represents a poor prognosticator in Merkel cell carcinomas that regulates oncoproteins, cell cycle arrest and SOX-2 expression.Scientific reports · 2025Article
- MDM2 promotes CELF6 ubiquitination-dependent degradation to promote neuroblastoma cell proliferation.Cell death & disease · 2025Article
- Selective targeting of genome amplifications and repeat elements by CRISPR-Cas9 nickases to promote cancer cell death.Nature communications · 2025Article
- Novel Compounds Target Aberrant Calcium Signaling in the Treatment of Relapsed High-Risk Neuroblastoma.International journal of molecular sciences · 2025Article
- Article
- Targeting the MYCN-MDM2 pathways for cancer therapy: Are they druggable?Genes & diseases · 2025Review
- MYCN as an oncogene in pediatric brain tumors.Frontiers in oncology · 2025Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
- MYC Drives mRNA Pseudouridylation to Mitigate Proliferation-Induced Cellular Stress during Cancer Development.Cancer research · 2024Article
- MDM2 inhibitors in cancer immunotherapy: Current status and perspective.Genes & diseases · 2024Review
- Induction of the Mdm2 gene and protein by kinase signaling pathways is repressed by the pVHL tumor suppressor.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A multi-omics approach for biomarker discovery in neuroblastoma: a network-based framework.NPJ systems biology and applications · 2024Article
- AF1q is a universal marker of neuroblastoma that sustains N-Myc expression and drives tumorigenesis.Oncogene · 2024Article
- Aryl hydrocarbon receptor is a tumor promoter iniScience · 2023Article
- Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches.International journal of molecular sciences · 2023Article
- A Review of the Regulatory Mechanisms of N-Myc on Cell Cycle.Molecules (Basel, Switzerland) · 2023Review
- Deciphering the Role of p53 and TAp73 in Neuroblastoma: From Pathogenesis to Treatment.Cancers · 2022Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The MYCN oncogene is the major negative prognostic marker in neuroblastoma with important roles in both the pathogenesis and clinical behavior of this aggressive malignancy. MYC oncogenes activate both proliferative and apoptotic cellular pathways and, accordingly, inhibition of p53-mediated apoptosis is a prerequisite for MYC-driven tumorigenesis. To identify novel transcriptional targets mediating the MYCN-dependent phenotype, we screened a MYCN-amplified neuroblastoma cell line by using chromatin immunoprecipitation (ChIP) cloning. We identified the essential p53 inhibitor and protooncogene MDM2 as a putative target. MDM2 has multiple p53-independent functions modulating cell cycle and transcriptional events. Standard ChIP with MYCN antibodies established the binding of MYCN to a consensus E-box within the human MDM2 promoter. Oligonucleotide pull-down assays further established the capacity of MYCN to bind to this promoter region, confirming the ChIP results. Luciferase reporter assays confirmed the E-box-specific, MYCN-dependent regulation of the MDM2 promoter in MYCN-inducible neuroblastoma cell lines. Real-time quantitative PCR and Western blot analysis demonstrated a rapid increase in endogenous MDM2 mRNA and MDM2 protein upon induction of MYCN. Targeted inhibition of MYCN in a MYCN-amplified neuroblastoma cell line resulted in decreased MDM2 expression levels with concomitant stabilization of p53 and induction of apoptosis. Our finding that MYCN directly modulates baseline MDM2 levels suggests a mechanism contributing to the pathogenesis of neuroblastoma and other MYC-driven malignancies through inhibition of MYC-stimulated apoptosis.
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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.