ArticleProceedings of the National Academy of Sciences of the United States of America2003
Functional mutants of the sequence-specific transcription factor p53 and implications for master genes of diversity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Clinicopathologic characteristics of brain tumors are associated with the presence and patterns of TP53 mutations: evidence from the IARC TP53 Database.Neuromolecular medicine · 2014Pooled it
- p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus.The Journal of clinical investigation · 2019Trial
- Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial.Breast cancer research : BCR · 2012Trial
- Altered-function p53 missense mutations identified in breast cancers can have subtle effects on transactivation.Molecular cancer research : MCR · 2010Trial
- Human P53 Expression in Yeast: Investigating Its Apoptotic Effects.Mini reviews in medicinal chemistry · 2026Review
- Epstein-Barr virus replication within differentiated epithelia requires pRb sequestration of activator E2F transcription factors.Journal of virology · 2024Article
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Review
- Characterisation of a novel transcript LNPPS acting as tumour suppressor in bladder cancer via PDCD5-mediated p53 degradation blockage.Clinical and translational medicine · 2023Article
- Article
- Mutant p53Frontiers in genetics · 2022Article
- Novel Allosteric Mechanism of Dual p53/MDM2 and p53/MDM4 Inhibition by a Small Molecule.Frontiers in molecular biosciences · 2022Article
- p66α Suppresses Breast Cancer Cell Growth and Migration by Acting as Co-Activator of p53.Cells · 2021Article
- Hidden electrostatic energy contributions define dynamic allosteric communications within p53 during molecular recognition.Biophysical journal · 2021Article
- Article
- Article
- Chaperones and Ubiquitin Ligases Balance Mutant p53 Protein Stability in Esophageal and Other Digestive Cancers.Cellular and molecular gastroenterology and hepatology · 2021Review
- A Protein in the YeastBiomolecules · 2020Article
- Heterogeneity ofFrontiers in oncology · 2020Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
Abstract
There are many sources of genetic diversity, ranging from programmed mutagenesis in antibody genes to random mutagenesis during species evolution or development of cancer. We propose that mutations in DNA sequence-specific transcription factors that target response elements (REs) in many genes can also provide for rapid and broad phenotypic diversity, if the mutations lead to altered binding affinities at individual REs. To test this concept, we examined the in vivo transactivation capacity of wild-type human and murine p53 and 25 partial function mutants. The p53s were expressed in yeast from a rheostatable promoter, and the transactivation capacities toward >15 promoter REs upstream of a reporter gene were measured. Surprisingly, there was wide variation in transactivation by the mutant p53s toward the various REs. This is the first study to address directly the impact of mutations in a sequence-specific transcription factor on transactivation from a wide array of REs. We propose a master gene hypothesis for phenotypic diversity where the master gene is a single transcriptional activator (or repressor) that regulates many genes through different REs. Mutations of the master gene can lead to a variety of simultaneous changes in both the selection of targets and the extent of transcriptional modulation at the individual targets, resulting in a vast number of potential phenotypes that can be created with minimal mutational changes without altering existing protein-protein interactions.
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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.