ArticleMolecular oncology2014
Tetramerization-defects of p53 result in aberrant ubiquitylation and transcriptional activity.
Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- A quantitative, Bayesian-informed approach to gene-specific variant classification: Updated Expert Panel recommendations improve classification of TP53 germline variants for Li-Fraumeni syndrome.Genome medicine · 2025Review
- Correlation of p53 oligomeric status and its subcellular localization in the presence of the AML-associated NPM mutant.PloS one · 2025Article
- p53: The Multifaceted Roles of Covalent Modifications in Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Review
- HER2 Antibody-Drug Conjugates Are Active against Desmoplastic Small Round Cell Tumor.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Germline variant affecting p53β isoforms predisposes to familial cancer.Nature communications · 2024Article
- The Ashkenazi-Centric G334R Variant ofMolecular and cellular biology · 2024Article
- Association ofmedRxiv : the preprint server for health sciences · 2023Article
- p53 and Its Isoforms in Renal Cell Carcinoma-Do They Matter?Biomedicines · 2022Review
- Review
- p53 tetramerization: at the center of the dominant-negative effect of mutant p53.Genes & development · 2020Review
- Article
- C-terminal region of human p53 attenuates buffalo p53 N-terminal-specific transactivation of p21 promoter by modulating tetramerization of the protein.Molecular and cellular biochemistry · 2018Article
- Wild-type and cancer-related p53 proteins are preferentially degraded by MDM2 as dimers rather than tetramers.Genes & development · 2018Article
- Analysis of defective protein ubiquitylation associated to adriamycin resistant cells.Cell cycle (Georgetown, Tex.) · 2017Article
- p53 oligomerization status modulates cell fate decisions between growth, arrest and apoptosis.Cell cycle (Georgetown, Tex.) · 2016Article
- Significance of TP53 Mutation in Wilms Tumors with Diffuse Anaplasia: A Report from the Children's Oncology Group.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Genomic profiling of multiple sequentially acquired tumor metastatic sites from an "exceptional responder" lung adenocarcinoma patient reveals extensive genomic heterogeneity and novel somatic variants driving treatment response.Cold Spring Harbor molecular case studies · 2016Article
- Tetramerization-defects of p53 result in aberrant ubiquitylation and transcriptional activity.Molecular oncology · 2014Article
Corrections and comments
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Authors and funding
16 authors at 8 institutions in 4 countries.
Funding
Abstract
The tumor suppressor p53 regulates the expression of genes involved in cell cycle progression, senescence and apoptosis. Here, we investigated the effect of single point mutations in the oligomerization domain (OD) on tetramerization, transcription, ubiquitylation and stability of p53. As predicted by docking and molecular dynamics simulations, p53 OD mutants show functional defects on transcription, Mdm2-dependent ubiquitylation and 26S proteasome-mediated degradation. However, mutants unable to form tetramers are well degraded by the 20S proteasome. Unexpectedly, despite the lower structural stability compared to WT p53, p53 OD mutants form heterotetramers with WT p53 when expressed transiently or stably in cells wild type or null for p53. In consequence, p53 OD mutants interfere with the capacity of WT p53 tetramers to be properly ubiquitylated and result in changes of p53-dependent protein expression patterns, including the pro-apoptotic proteins Bax and PUMA under basal and adriamycin-induced conditions. Importantly, the patient derived p53 OD mutant L330R (OD1) showed the more severe changes in p53-dependent gene expression. Thus, in addition to the well-known effects on p53 stability, ubiquitylation defects promote changes in p53-dependent gene expression with implications on some of its functions.
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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.