ArticleOncogene2020
Mdm4 supports DNA replication in a p53-independent fashion.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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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
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- MDM2 binds and suppresses RNA polymerase III to restrain the innate immune response to cytosolic DNA.Cell death and differentiation · 2026Article
- MDM4 at the Crossroads: Beyond p53 and MDM2.Cancers · 2026Review
- Dependence on Mdm2 for Mdm4 inhibition of p53 activity.Cancer letters · 2025Article
- SNRPB2 promotes triple-negative breast cancer progression by controlling alternative splicing of MDM4 pre-mRNA.Cancer science · 2024Article
- MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers.European journal of medical research · 2024Article
- MDMX in Cancer: A Partner of p53 and a p53-Independent Effector.Biologics : targets & therapy · 2024Review
- Poison cassette exon splicing of SRSF6 regulates nuclear speckle dispersal and the response to hypoxia.Nucleic acids research · 2023Article
- MDMX elevation by a novel Mdmx-p53 interaction inhibitor mitigates neuronal damage after ischemic stroke.Scientific reports · 2022Article
- Targeting MDM4 as a Novel Therapeutic Approach in Prostate Cancer Independent of p53 Status.Cancers · 2022Article
- MDM2-Driven Ubiquitination Rapidly Removes p53 from Its Cognate Promoters.Biomolecules · 2021Article
- Article
- The roles and regulation of MDM2 and MDMX: it is not just about p53.Genes & development · 2021Review
- The integrated stress response induces R-loops and hinders replication fork progression.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The Mdm4 (alias MdmX) oncoprotein, like its paralogue and interaction partner Mdm2, antagonizes the tumor suppressor p53. p53-independent roles of the Mdm proteins are emerging, and we have reported the ability of Mdm2 to modify chromatin and to support DNA replication by suppressing the formation of R-loops (DNA/RNA-hybrids). We show here that the depletion of Mdm4 in p53-deficient cells compromises DNA replication fork progression as well. Among various deletion mutants, only full-length Mdm4 was able to support DNA replication fork progression. Co-depletion of Mdm4 and Mdm2 further impaired DNA replication, and the overexpression of each partially compensated for the other's loss. Despite impairing replication, Mdm4 depletion only marginally hindered cell proliferation, likely due to compensation through increased firing of replication origins. However, depleting Mdm4 sensitized p53-/- cells to the nucleoside analog gemcitabine, raising the future perspective of using Mdm4 inhibitors as chemosensitizers. Mechanistically, Mdm4 interacts with members of the Polycomb Repressor Complexes and supports the ubiquitination of H2A, thereby preventing the accumulation of DNA/RNA-hybrids. Thus, in analogy to previously reported activities of Mdm2, Mdm4 enables unperturbed DNA replication through the avoidance of R-loops.
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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.