ArticleOncogene2010
Regulation of MDM4 (MDMX) function by p76(MDM2): a new facet in the control of p53 activity.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
- Fbrsl1 is required for cranial neural crest development and reflects a conserved function of the human disease-associated protein.Disease models & mechanisms · 2025Article
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.Disease models & mechanisms · 2024Article
- Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex.Nature communications · 2022Article
- Emerging concepts underlying selective neuromuscular dysfunction in infantile-onset spinal muscular atrophy.Neural regeneration research · 2021Review
- Mutation in Eftud2 causes craniofacial defects in mice via mis-splicing of Mdm2 and increased P53.Human molecular genetics · 2021Article
- Zmat3 Is a Key Splicing Regulator in the p53 Tumor Suppression Program.Molecular cell · 2020Article
- Dysregulation of Mdm2 and Mdm4 alternative splicing underlies motor neuron death in spinal muscular atrophy.Genes & development · 2018Article
- Article
- The alternative translated MDMX(p60) isoform regulates MDM2 activity.Cell cycle (Georgetown, Tex.) · 2015Article
- A Molecular Biological and Biochemical Investigation on Mycobacterium tuberculosis MutT Protein.Jundishapur journal of microbiology · 2014Article
- Phospho-ΔNp63α/miR-885-3p axis in tumor cell life and cell death upon cisplatin exposure.Cell cycle (Georgetown, Tex.) · 2011Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Under basal growth conditions, p53 function is tightly controlled by the members of MDM family, MDM2 and MDM4. The Mdm2 gene codes, in addition to the full-length p90(MDM2), for a short protein, p76(MDM2) that lacks the p53-binding domain. Despite this property and at variance with p90(MDM2), this protein acts positively toward p53, although the molecular mechanism remains elusive. Here, we report that p76(MDM2) antagonizes MDM4 inhibitory function. We show that p76(MDM2) possesses intrinsic ubiquitinating and degrading activity, and through these activities controls MDM4 levels. Furthermore, the presence of p76(MDM2) decreases the association of MDM4 with p53 and p90(MDM2), and antagonizes p53 degradation by the heterodimer MDM4/p90(MDM2). The p76(MDM2)-mediated regulation of MDM4 occurs in the cytoplasm, under basal growth conditions. Conversely, upon DNA damage, phosphorylation of MDM4Ser403 dissociates p76(MDM2) and prevents MDM4 degradation. The overall negative control of MDM4 by p76(MDM2) reflects on p53 function as p76(MDM2) impairs MDM4-mediated inhibition of p53 activity. In agreement with the positive role of p76(MDM2) toward p53, the p76(MDM2)/p90(MDM2) ratio significantly decreases in a group of thyroid tumor samples compared with normal counterparts. Overall, these findings reveal a new mechanism in the control of p53 basal activity that may account for the distinct sensitivity of tissues to stress signals depending on the balance among MDM proteins. Moreover, these data suggest an oncosuppressive function for a product of the Mdm2 gene.
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