ArticleGenes & development2016
The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans.
Article in Genes & development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Mitochondrial dynamics imbalance in hepatocellular carcinoma: from molecular mechanisms to new strategies for targeted therapy.Translational cancer research · 2026Review
- A cancer persistent DNA repair circuit driven by MDM2, MDM4 (MDMX), and mutant p53 for recruitment of MDC1 and 53BP1 on chromatin.Nucleic acids research · 2025Article
- Evolution of affinity between p53 transactivation domain and MDM2 across the animal kingdom demonstrates high plasticity of motif-mediated interactions.Protein science : a publication of the Protein Society · 2023Article
- TP53 and its Regulatory Genes as Prognosis of Cutaneous Melanoma.Cancer informatics · 2023Article
- The Elephant Evolved p53 Isoforms that Escape MDM2-Mediated Repression and Cancer.Molecular biology and evolution · 2022Article
- Evolutionary history of the p53 family DNA-binding domain: insights from an Alvinella pompejana homolog.Cell death & disease · 2022Article
- Increased risk of cancer in dogs and humans: a consequence of recent extension of lifespan beyond evolutionarily-determined limitations?Aging and cancer · 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
- Identification of a Catalytic Active but Non-Aggregating MDM2 RING Domain Variant.Journal of molecular biology · 2021Article
- Nutlin-Induced Apoptosis Is Specified by a Translation Program Regulated by PCBP2 and DHX30.Cell reports · 2020Article
- Lampreys, the jawless vertebrates, contain three Pax6 genes with distinct expression in eye, brain and pancreas.Scientific reports · 2019Article
- Shaping the regulation of the p53 mRNA tumour suppressor: the co-evolution of genetic signatures.BMC cancer · 2019Review
- A single synonymous mutation determines the phosphorylation and stability of the nascent protein.Journal of molecular cell biology · 2019Article
- Silencing of Xeroderma Pigmentosum Group D Gene Promotes Hepatoma Cell Growth by Reducing P53 Expression.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Review
- HMGB1 represses the anti-cancer activity of sunitinib by governing TP53 autophagic degradation via its nucleus-to-cytoplasm transport.Autophagy · 2018Article
- Identification of XBP1-u as a novel regulator of the MDM2/p53 axis using an shRNA library.Science advances · 2017Article
- Voltage-gated sodium channel gene repertoire of lampreys: gene duplications, tissue-specific expression and discovery of a long-lost gene.Proceedings. Biological sciences · 2017Article
- Lampreys, the jawless vertebrates, contain only two ParaHox gene clusters.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Evolution of the p53-MDM2 pathway.BMC evolutionary biology · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The extant jawless vertebrates, represented by lampreys and hagfish, are the oldest group of vertebrates and provide an interesting genomic evolutionary pivot point between invertebrates and jawed vertebrates. Through genome analysis of one of these jawless vertebrates, the Japanese lamprey (Lethenteron japonicum), we identified all three members of the important p53 transcription factor family--Tp53, Tp63, and Tp73--as well as the Mdm2 and Mdm4 genes. These genes and their products are significant cellular regulators in human cancer, and further examination of their roles in this most distant vertebrate relative sheds light on their origin and coevolution. Their important role in response to DNA damage has been highlighted by the discovery of multiple copies of the Tp53 gene in elephants. Expression of lamprey p53, Mdm2, and Mdm4 proteins in mammalian cells reveals that the p53-Mdm2 interaction and the Mdm2/Mdm4 E3 ligase activity existed in the common ancestor of vertebrates and have been conserved for >500 million years of vertebrate evolution. Lamprey Mdm2 degrades human p53 with great efficiency, but this interaction is not blocked by currently available small molecule inhibitors of the human HDM2 protein, suggesting utility of lamprey Mdm2 in the study of the human p53 signaling pathway.
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