ArticleThe EMBO journal2009
MDM4 (MDMX) localizes at the mitochondria and facilitates the p53-mediated intrinsic-apoptotic pathway.
Article in The EMBO journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 77 citations in OpenAlex.
- A membrane-penetrating modified ascites-derived peptide, TAT-CPAP1, sensitizes TP53 wild-type ovarian cancer cells to platinum-based therapy through targeting the NOLC1-MDM2/MDM4 axis.Translational oncology · 2026Article
- Implicating Sperm microRNA hsa-miR-7977 and its Target Genes in Idiopathic Recurrent Pregnancy Loss: Evidence from Expression Analysis.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- Targeting the MDM2-MDM4 interaction interface reveals an otherwise therapeutically active wild-type p53 in colorectal cancer.Molecular oncology · 2025Article
- MDMX enhances radiosensitivity in lung adenocarcinoma and squamous cell carcinoma by inhibiting P53-mediated autophagy.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- ROSBASE1.0: a comprehensive database of reactive oxygen species (ROS): categorization of cell organelles, proteins, taxonomy, and diseases based on ROS-related activities.Database : the journal of biological databases and curation · 2025Article
- Low glucose metabolite 3-phosphoglycerate switches PHGDH from serine synthesis to p53 activation to control cell fate.Cell research · 2023Article
- The ARTS of p53-dependent mitochondrial apoptosis.Journal of molecular cell biology · 2023Review
- Progression of the pluripotent epiblast depends upon the NMD factor UPF2.Development (Cambridge, England) · 2022Article
- Inhibition of the mTOR pathway and reprogramming of protein synthesis by MDM4 reduce ovarian cancer metastatic properties.Cell death & disease · 2021Article
- Review
- Review
- Low Expression of SLC7A11 Confers Drug Resistance and Worse Survival in Ovarian CancerFrontiers in oncology · 2021Article
- Making Connections: p53 and the Cathepsin Proteases as Co-Regulators of Cancer and Apoptosis.Cancers · 2020Review
- HOPS and p53: thick as thieves in life and death.Cell cycle (Georgetown, Tex.) · 2020Review
- Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy.International journal of molecular sciences · 2020Review
- Targeting MDMX for Cancer Therapy: Rationale, Strategies, and Challenges.Frontiers in oncology · 2020Review
- Estrogens Counteract Platinum-Chemosensitivity by Modifying the Subcellular Localization of MDM4.Cancers · 2019Article
- The long and the short of it: the MDM4 tail so far.Journal of molecular cell biology · 2019Review
- Mitochondrial MDM2 Regulates Respiratory Complex I Activity Independently of p53.Molecular cell · 2018Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MDM4 is a key regulator of p53, whose biological activities depend on both transcriptional activity and transcription-independent mitochondrial functions. MDM4 binds to p53 and blocks its transcriptional activity; however, the main cytoplasmic localization of MDM4 might also imply a regulation of p53-mitochondrial function. Here, we show that MDM4 stably localizes at the mitochondria, in which it (i) binds BCL2, (ii) facilitates mitochondrial localization of p53 phosphorylated at Ser46 (p53Ser46(P)) and (iii) promotes binding between p53Ser46(P) and BCL2, release of cytochrome C and apoptosis. In agreement with these observations, MDM4 reduction by RNA interference increases resistance to DNA-damage-induced apoptosis in a p53-dependent manner and independently of transcription. Consistent with these findings, a significant downregulation of MDM4 expression associates with cisplatin resistance in human ovarian cancers, and MDM4 modulation affects cisplatin sensitivity of ovarian cancer cells. These data define a new localization and function of MDM4 that, by acting as a docking site for p53Ser46(P) to BCL2, facilitates the p53-mediated intrinsic-apoptotic pathway. Overall, our results point to MDM4 as a double-faced regulator of p53.
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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.