Evidence map›Paper›PMID 36433934›Full record

ArticleCell death & disease2022

Translational readthrough of nonsense mutant TP53 by mRNA incorporation of 5-Fluorouridine.

Mireia Palomar-Siles, Angelos Heldin, Meiqiongzi Zhang, Charlotte Strandgren, Viktor Yurevych, Jip T van Dinter, Sem A G Engels, Damon A Hofman, Susanne Öhlin, Birthe Meineke and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 31 citations in OpenAlex.

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  16. Therapeutic targeting ofUpsala journal of medical sciences · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Mireia Palomar-SilesDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Angelos HeldinDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Meiqiongzi ZhangDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Charlotte StrandgrenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Viktor YurevychPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0003-2805-2454
Jip T van DinterPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Sem A G EngelsPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
Damon A HofmanPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0003-4411-4563
Susanne ÖhlinDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Birthe MeinekeDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Vladimir J N BykovDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7199-8942
Sebastiaan van HeeschPrincess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.ORCID 0000-0001-9593-1980
Klas G WimanDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Klas.Wiman@ki.se.ORCID 0000-0002-7113-524X
Karolinska Institutet · SEPrincess Máxima Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

TP53 nonsense mutations in cancer produce truncated inactive p53 protein. We show that 5-FU metabolite 5-Fluorouridine (FUr) induces full-length p53 in human tumor cells carrying R213X nonsense mutant TP53. Ribosome profiling visualized translational readthrough at the R213X premature stop codon and demonstrated that FUr-induced readthrough is less permissive for canonical stop codon readthrough compared to aminoglycoside G418. FUr is incorporated into mRNA and can potentially base-pair with guanine, allowing insertion of Arg tRNA at the TP53 R213X UGA premature stop codon and translation of full-length wild-type p53. We confirmed that full-length p53 rescued by FUr triggers tumor cell death by apoptosis. FUr also restored full-length p53 in TP53 R213X mutant human tumor xenografts in vivo. Thus, we demonstrate a novel strategy for therapeutic rescue of nonsense mutant TP53 and suggest that FUr should be explored for treatment of patients with TP53 nonsense mutant tumors.

Indexed as

NeoplasmsTumor Suppressor Protein p53Codon, NonsenseHumansProtein BiosynthesisRNA, MessengerUridine5-fluorouridineCodon, NonsenseRNA, MessengerTP53 protein, humanTumor Suppressor Protein p53Uridine

Identifiers

PMID36433934
PMCPMC9700717
OpenAlexW4310062322

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.