ArticleThe Journal of biological chemistry2012
Chaperoning of mutant p53 protein by wild-type p53 protein causes hypoxic tumor regression.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Pseudo-mutant P53 is a unique phenotype ofHaematologica · 2022Article
- GOF Mutant p53 in Cancers: A Therapeutic Challenge.Cancers · 2022Review
- Anticancer Therapeutic Strategies Targeting p53 Aggregation.International journal of molecular sciences · 2022Review
- Allele-specific genomic data elucidate the role of somatic gain and copy-number neutral loss of heterozygosity in cancer.Cell systems · 2022Article
- Tumorigenic p53 mutants undergo common structural disruptions including conversion to α-sheet structure.Protein science : a publication of the Protein Society · 2020Article
- Amplifying Tumor-Stroma Communication: An Emerging Oncogenic Function of Mutant p53.Frontiers in oncology · 2020Review
- The Diverse Functions of Mutant 53, Its Family Members and Isoforms in Cancer.International journal of molecular sciences · 2019Review
- HIF-transcribed p53 chaperones HIF-1α.Nucleic acids research · 2019Article
- Article
- The curcumin analog HO-3867 selectively kills cancer cells by converting mutant p53 protein to transcriptionally active wildtype p53.The Journal of biological chemistry · 2018Article
- Combining p53 stabilizers with metformin induces synergistic apoptosis through regulation of energy metabolism in castration-resistant prostate cancer.Cell cycle (Georgetown, Tex.) · 2016Article
- Tip110 Regulates the Cross Talk between p53 and Hypoxia-Inducible Factor 1α under Hypoxia and Promotes Survival of Cancer Cells.Molecular and cellular biology · 2015Article
- Mutant p53 in cancer: new functions and therapeutic opportunities.Cancer cell · 2014Review
- p53's choice of myocardial death or survival: Oxygen protects infarct myocardium by recruiting p53 on NOS3 promoter through regulation of p53-Lys(118) acetylation.EMBO molecular medicine · 2013Article
- Cross-talk between HIF and p53 as mediators of molecular responses to physiological and genotoxic stresses.Molecular cancer · 2013Review
- The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2).The Journal of biological chemistry · 2013Article
- SCO2 induces p53-mediated apoptosis by Thr845 phosphorylation of ASK-1 and dissociation of the ASK-1-Trx complex.Molecular and cellular biology · 2013Article
- Re-oxygenation causes hypoxic tumor regression through restoration of p53 wild-type conformation and post-translational modifications.Cell death & disease · 2012Article
- Regulation of glucose metabolism by p53: emerging new roles for the tumor suppressor.Oncotarget · 2011Review
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 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutant (Mt) p53 abrogates tumor suppression functions of wild-type (WT) p53 through mutant-specific, gain-of-function effects, and patients bearing Mt p53 are chemoresistant. The dominant negative effect of p53 mutants results from their aggregation propensity which causes co-aggregation of WT p53. We explored the mechanism of p53 inactivation in hypoxia and hypothesized whether WT p53 could rescue Mt p53 in hypoxic tumors. WT p53 exists in mutant conformation in hypoxic core of MCF-7 solid tumors, and its conformation is oxygen-dependent. Under simulated hypoxia in cells, WT p53 undergoes conformational change in acquiring mutant conformation. An in vivo chaperone assay shows that WT p53 functions as a molecular chaperone in rescuing conformational and structural p53 mutants in cancer cells both at the transcription and proteome levels. WT p53 chaperone therapy is further shown to cause significant regression of tumor xenografts through reconversion of the mutant phenotype to wild-type p53. The chaperone function of WT p53 is directly linked to the induction of apoptosis in both cancer cells and tumor xenografts. As oncogenic p53 mutants are linked to chemoresistance in hypoxic tumors, p53 chaperone therapy will introduce new dimensions to existing cancer therapeutics. We propose that in cancer cells, WT p53 chaperoning may either exist as a cellular event to potentially reverse the dominant negative effect of its oncogenic mutants or to stabilize yet unidentified factors.
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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.