ArticleNucleic acids research2021
The MDM2 inducible promoter folds into four-tetrad antiparallel G-quadruplexes targetable to fight malignant liposarcoma.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Detangling knots: the intricate roles of G-quadruplexes in herpesvirus replication.Journal of virology · 2026Review
- G‑Quadruplex and i‑Motif Structures in theACS omega · 2026Article
- Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.Research (Washington, D.C.) · 2026Review
- Chromatin Immunoprecipitation Reveals p53 Binding to G-Quadruplex DNA Sequences in Myeloid Leukemia Cell Lines.ACS bio & med chem Au · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- The G-quadruplex experimental drug QN-302 impairs liposarcoma cell growth by inhibiting MDM2 expression and restoring p53 levels.Nucleic acids research · 2025Article
- A Phenotypic Approach to the Discovery of Potent G-Quadruplex Targeted Drugs.Molecules (Basel, Switzerland) · 2024Review
- Bioactive nutraceuticals as G4 stabilizers: potential cancer prevention and therapy-a critical review.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis.Nature communications · 2024Article
- EndoQuad: a comprehensive genome-wide experimentally validated endogenous G-quadruplex database.Nucleic acids research · 2024Article
- Targeting liposarcoma: unveiling molecular pathways and therapeutic opportunities.Frontiers in oncology · 2024Review
- Review
- Improving the accuracy of the FMO binding affinity prediction of ligand-receptor complexes containing metals.Journal of computer-aided molecular design · 2023Article
- G-quadruplex DNA contributes to RNA polymerase II-mediated 3D chromatin architecture.Nucleic acids research · 2023Article
- Genome-wide mapping of i-motifs reveals their association with transcription regulation in live human cells.Nucleic acids research · 2023Article
- The FMO2 analysis of the ligand-receptor binding energy: the Biscarbene-Gold(I)/DNA G-Quadruplex case study.Journal of computer-aided molecular design · 2022Article
- TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin.Nucleic acids research · 2022Article
- Interaction between non-coding RNAs, mRNAs and G-quadruplexes.Cancer cell international · 2022Review
- Major Achievements in the Design of Quadruplex-Interactive Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Well-differentiated liposarcoma (WDLPS) is a malignant neoplasia hard to diagnose and treat. Its main molecular signature is amplification of the MDM2-containing genomic region. The MDM2 oncogene is the master regulator of p53: its overexpression enhances p53 degradation and inhibits apoptosis, leading to the tumoral phenotype. Here, we show that the MDM2 inducible promoter G-rich region folds into stable G-quadruplexes both in vitro and in vivo and it is specifically recognized by cellular helicases. Cell treatment with G-quadruplex-ligands reduces MDM2 expression and p53 degradation, thus stimulating cancer cell cycle arrest and apoptosis. Structural characterization of the MDM2 G-quadruplex revealed an extraordinarily stable, unique four-tetrad antiparallel dynamic conformation, amenable to selective targeting. These data indicate the feasibility of an out-of-the-box G-quadruplex-targeting approach to defeat WDLPS and all tumours where restoration of wild-type p53 is sought. They also point to G-quadruplex-dependent genomic instability as possible cause of MDM2 expansion and WDLPS tumorigenesis.
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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.