ArticleGene2011
The evolution of MDM2 family genes.
Article in Gene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Structure and function of MDM2 and MDM4 in health and disease.The Biochemical journal · 2025Review
- High-Throughput Discovery of Substrate Peptide Sequences for E3 Ubiquitin Ligases Using a cDNA Display Method.Chembiochem : a European journal of chemical biology · 2024Article
- Insights into the Interaction Mechanisms of Peptide and Non-Peptide Inhibitors with MDM2 Using Gaussian-Accelerated Molecular Dynamics Simulations and Deep Learning.Molecules (Basel, Switzerland) · 2024Article
- Cell quiescence in planarian stem cells, interplay between p53 and nutritional stimuli.Open biology · 2022Article
- Evolutionary history of the p53 family DNA-binding domain: insights from an Alvinella pompejana homolog.Cell death & disease · 2022Article
- It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy.Frontiers in cell and developmental biology · 2022Review
- Towards reconstructing the dipteran demise of an ancient essential gene: E3 ubiquitin ligase Murine double minute.Development genes and evolution · 2020Article
- Mdm4 supports DNA replication in a p53-independent fashion.Oncogene · 2020Article
- Exon 3 of theG3 (Bethesda, Md.) · 2019Article
- Review
- Tan IIA inhibits H1299 cell viability through the MDM4‑IAP3 signaling pathway.Molecular medicine reports · 2018Article
- Emodin promotes the arrest of human lymphoma Raji cell proliferation through the UHRF1‑DNMT3A‑∆Np73 pathways.Molecular medicine reports · 2017Article
- The Role of MDM2 in Promoting Genome Stability versus Instability.International journal of molecular sciences · 2017Review
- The Functional Roles of the MDM2 Splice Variants P2-MDM2-10 and MDM2-∆5 in Breast Cancer Cells.Translational oncology · 2017Article
- Evolution of the p53-MDM2 pathway.BMC evolutionary biology · 2017Article
- Impact of the MDM2 splice-variants MDM2-A, MDM2-B and MDM2-C on cytotoxic stress response in breast cancer cells.BMC cell biology · 2017Article
- Anatomy of Mdm2 and Mdm4 in evolution.Journal of molecular cell biology · 2017Review
- MDM2 oligomers: antagonizers of the guardian of the genome.Oncogene · 2016Review
- Functional characterization of p53 pathway components in the ancient metazoan Trichoplax adhaerens.Scientific reports · 2016Article
- The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans.Genes & development · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
MDM2 and MDM4 are proto-oncoproteins that bind to and inhibit members of the p53 protein family, p53, p73 and possibly p63. p53 is a mammalian tumor suppressor and p63 and p73 are critical for development. With the sequencing of genomes from multiple organisms there is mounting evidence for a consensus scenario of p53 gene family evolution. A single p53/p63/p73 gene is in invertebrates and required for maintenance of germline DNA. Gene duplication occurred in an ancestor in common with cartilaginous fishes, giving rise to a separate p53 gene and at least one ancestral p63/p73 gene. In bony vertebrates, all three p53 gene family paralogs, p53, p63, and p73 are distinct genes. This raises the question of how MDM2 and MDM4 genes evolved. We show evidence that MDM2 and MDM4 arose from a gene duplication event prior to the emergence of bony vertebrates more than 440 millionyears ago. Comparative genome studies indicate that invertebrate organisms have only one MDM homolog. In jawed vertebrates, the p53-binding domains of MDM2 and MDM4 proteins evolved at a high rate, approaching the evolution rate of the MDM2-binding domain of p53. However, the MDM2-binding domain of p73 exhibits markedly stronger conservation suggesting novel p53-independent functions. The most conserved domain within all MDM2 family members is the RING domain of the MDM2 ortholog which is responsible for ubiquitination of p53 and heterodimerization with MDM4. We suggest a model where oligomerization is an ancient function of MDM and ubiquitination activity was acquired later near the MDM gene duplication event coinciding with the time of the emergence of p53 as a distinct gene.
Indexed as
Identifiers
What OpenQuestion holds
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.