ArticleProceedings of the National Academy of Sciences of the United States of America1996
Mutant conformation of p53 translated in vitro or in vivo requires functional HSP90.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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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
117 citing papers in PubMed, 315 citations in OpenAlex.
- Expression of Heat Shock Protein 70 Gene and Its Correlation with Inflammatory Markers in Essential Hypertension.PloS one · 2016Trial
- Pre-clinical efficacy of PU-H71, a novel HSP90 inhibitor, alone and in combination with bortezomib in Ewing sarcoma.Molecular oncology · 2014Trial
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- Review
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- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
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- Natural Products Targeting Hsp90 for a Concurrent Strategy in Glioblastoma and Neurodegeneration.Metabolites · 2022Review
- Combination of AURKA inhibitor and HSP90 inhibitor to treat breast cancer with AURKA overexpression and TP53 mutations.Medical oncology (Northwood, London, England) · 2022Review
- Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance.Cells · 2022Review
- Emerging Link between Tsc1 and FNIP Co-Chaperones of Hsp90 and Cancer.Biomolecules · 2022Review
- Host cell stress response as a predictor of COVID-19 infectivity and disease progression.Frontiers in molecular biosciences · 2022Review
- TP53 in Myelodysplastic Syndromes.Cancers · 2021Review
- Selective functional inhibition of a tumor-derived p53 mutant by cytosolic chaperones identified using split-YFP in budding yeast.G3 (Bethesda, Md.) · 2021Article
- Suppression of HSF1 activity by wildtype p53 creates a driving force for p53 loss-of-heterozygosity.Nature communications · 2021Article
- Extracellular Vesicles: Messengers of p53 in Tumor-Stroma Communication and Cancer Metastasis.International journal of molecular sciences · 2020Review
- The molecular chaperone Hsp90 maintains Golgi organization and vesicular trafficking by regulating microtubule stability.Journal of molecular cell biology · 2020Article
- Tetra-substituted pyrrole derivatives act as potent activators of p53 in melanoma cells.Investigational new drugs · 2020Article
- Cancer Stemness: p53 at the Wheel.Frontiers in oncology · 2020Review
- The expression profiles and prognostic values of HSPs family members in Head and neck cancer.Cancer cell international · 2020Article
57 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
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 mutant, 143ala, was translated in vitro in either rabbit reticulocyte lysate (RRL) or wheat germ extract (WGE). In RRL, p53-143ala protein of both mutant and wild-type conformation, as detected immunologically with conformation-specific antibodies, was translated. The chaperone protein HSP90, present in RRL, was found to coprecipitate only with the mutated conformation of p53. Geldanamycin, shown previously to bind to HSP90 and destabilize its association with other proteins, decreased the amount of immunologically detectable mutated p53 and increased the amount of detectable wild-type protein, without affecting the total translation of p53. When translated in WGE, known to contain functionally deficient HSP90, p53-143ala produced p53 protein, which was not recognized by a mutated conformation-specific antibody. In contrast, the synthesis of conformationally detectable wild-type p53 in this system was not compromised. Reconstitution of HSP90 function in WGE permitted synthesis of conformationally detectable mutated p53, and this was abrogated by geldanamycin. Finally, when p53-143ala was stably tansfected into yeast engineered to be defective for HSP90 function, conformational recognition of mutated p53 was impaired. When stable transfectants of p53-143ala were prepared in yeast expressing wild-type HSP90, conformational recognition of mutated p53 was antagonized by macbecin I, a geldanamycin analog also known to bind HSP90. Taken together, these data demonstrate a role for HSP90 in the achievement and/or stabilization of the mutated conformation of p53-143ala. Furthermore, we show that the mutated conformation of p53 can be pharmacologically antagonized by drugs targeting HSP90.
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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.