ArticleOncogene2019
MDM2 promotes genome instability by ubiquitinating the transcription factor HBP1.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 50 citations in OpenAlex.
- The novel thioredoxin reductase inhibitor butaselen suppresses lung cancer by inducing oxidative stress.Redox report : communications in free radical research · 2025Article
- Methylation of RBM39 by PRMT6 enhances resistance to Indisulam in non-small cell lung cancer by promoting alternative splicing of proto-oncogenes.PLoS biology · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- Targeting apoptotic pathways for cancer therapy.The Journal of clinical investigation · 2024Review
- MDM2 provides TOP2 poison resistance by promoting proteolysis of TOP2βcc in a p53-independent manner.Cell death & disease · 2024Article
- MDM2 Implications for Potential Molecular Pathogenic Therapies of Soft-Tissue Tumors.Journal of clinical medicine · 2023Review
- Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT.Scientific reports · 2022Article
- Methylation of HBP1 by PRMT1 promotes tumor progression by regulating actin cytoskeleton remodeling.Oncogenesis · 2022Article
- Structural studies of antitumor compounds that target the RING domain of MDM2.Protein science : a publication of the Protein Society · 2022Article
- Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma.Frontiers in oncology · 2022Review
- CUL3 (cullin 3)-mediated ubiquitination and degradation of BECN1 (beclin 1) inhibit autophagy and promote tumor progression.Autophagy · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression.Journal of experimental & clinical cancer research : CR · 2021Article
- Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2021Article
- Identification of New Genes Involved in Germline Predisposition to Early-Onset Gastric Cancer.International journal of molecular sciences · 2021Article
- Identification and Validation of a Novel Genomic Instability-Associated Long Non-Coding RNA Prognostic Signature in Head and Neck Squamous Cell Carcinoma.Frontiers in cell and developmental biology · 2021Article
- Recent advances in the understanding and management of liposarcoma.Faculty reviews · 2021Review
- Identification of a Novel Prognostic Signature of Genome Instability-Related LncRNAs in Early Stage Lung Adenocarcinoma.Frontiers in cell and developmental biology · 2021Article
- Molecular and Biochemical Techniques for Deciphering p53-MDM2 Regulatory Mechanisms.Biomolecules · 2020Review
- Regulating tumor suppressor genes: post-translational modifications.Signal transduction and targeted therapy · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genome instability is a common feature of tumor cells, and the persistent presence of genome instability is a potential mechanism of tumorigenesis. The E3 ubiquitin ligase MDM2 is intimately involved in genome instability, but its mechanisms are unclear. Our data demonstrated that the transcription factor HBP1 is a target of MDM2. MDM2 facilitates HBP1 proteasomal degradation by ubiquitinating HBP1, regardless of p53 status, thus attenuating the transcriptional inhibition of HBP1 in the expression of its target genes, such as the DNA methyltransferase DNMT1 and histone methyltransferase EZH2, which results in global DNA hypermethylation and histone hypermethylation and ultimately genome instability. The repression of HBP1 by MDM2 finally promotes cell growth and tumorigenesis. Next, we thoroughly explored the regulatory mechanism of the MDM2/HBP1 axis in DNA damage repair following ionizing radiation. Our data indicated that MDM2 overexpression-mediated repression of HBP1 delays DNA damage repair and causes cell death in a p53-independent manner. This investigation elucidated the mechanism of how MDM2 promotes genome instability and enhances tumorigenesis in the absence of p53, thus providing a theoretical and experimental basis for targeting MDM2 as a cancer therapy.
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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.