ArticleOncogene2019
MDM2-mediated degradation of WRN promotes cellular senescence in a p53-independent manner.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 33 citations in OpenAlex.
- The expanding MDM2 universe.Cell death and differentiation · 2026Article
- Differential DNA damage response to WRN inhibition identifies a targetable vulnerability inScience advances · 2026Article
- Structure, Mutation, Functional Domain Roles and Medical Implications of Glycerol Kinase.The protein journal · 2026Review
- Structural insights into WRN helicase reveal conformational states and opportunities for MSI-H cancer drug discovery.Communications biology · 2026Article
- Suppression of MRPL23 induces cellular senescence in hepatocellular carcinoma by targeting HMGB1.Discover oncology · 2025Article
- MDM2 accelerated renal senescence via ubiquitination and degradation of HDAC1.Acta pharmacologica Sinica · 2024Article
- Response to Replication Stress and Maintenance of Genome Stability by WRN, the Werner Syndrome Protein.International journal of molecular sciences · 2024Review
- WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis.Nature communications · 2024Article
- Molecular characterization, clinical value, and cancer-immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer.Discover oncology · 2024Article
- Advancements in MDM2 inhibition: Clinical and pre-clinical investigations of combination therapeutic regimens.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Cellular senescence throws new insights into patient classification and pharmacological interventions for clinical management of hepatocellular carcinoma.World journal of gastrointestinal oncology · 2023Article
- MDM2- an indispensable player in tumorigenesis.Molecular biology reports · 2023Review
- Peripubertal Nutritional Prevention of Cancer-Associated Gene Expression and Phenotypes.Cancers · 2023Article
- Cellular Senescence: Mechanisms and Therapeutic Potential.Biomedicines · 2021Review
- Ferroptosis, radiotherapy, and combination therapeutic strategies.Protein & cell · 2021Review
- Piperlongumine inhibits migration and proliferation of castration-resistant prostate cancer cells via triggering persistent DNA damage.BMC complementary medicine and therapies · 2021Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2021Article
- Article
- Cellular senescence in hepatocellular carcinoma induced by a long non-coding RNA-encoded peptide PINT87aa by blocking FOXM1-mediatedTheranostics · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
MDM2 (Murine double minute 2) acts as a key repressor for p53-mediated tumor-suppressor functions, which includes cellular senescence. We found that MDM2 can promote cellular senescence by modulating WRN stability. Werner syndrome (WS), caused by mutations of the WRN gene, is an autosomal recessive disease, which is characterized by premature aging. Loss of WRN function induces cellular senescence in human cancer cells. Here, we found that MDM2 acts as an E3 ligase for WRN protein. MDM2 interacts with WRN both in vivo and in vitro. MDM2 induces ubiquitination of WRN and dramatically downregulates the levels of WRN protein in human cells. During DNA damage response, WRN is translocated to the nucleoplasm to facilitate its DNA repair functions; however, it is degraded by the MDM2-mediated ubiquitination pathway. Moreover, the senescent phenotype induced by DNA damage reagents, such as Etoposide, is at least in part mediated by MDM2-dependent WRN degradation as it can be significantly attenuated by ectopic expression of WRN. These results show that MDM2 is critically involved in regulating WRN function via ubiquitin-dependent degradation and reveal an unexpected role of MDM2 in promoting cellular senescence through a p53-independent manner.
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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.