Evidence map›Paper›PMID 26560363›Full record

ArticleScientific reports2015

Regulation of iron homeostasis by the p53-ISCU pathway.

Yuki Funauchi, Chizu Tanikawa, Paulisally Hau Yi Lo, Jinichi Mori, Yataro Daigo, Atsushi Takano, Yohei Miyagi, Atsushi Okawa, Yusuke Nakamura, Koichi Matsuda

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

70 citing papers in PubMed, 104 citations in OpenAlex.

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  19. Integrative Computational Framework,bioRxiv : the preprint server for biology · 2024
    Article
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10 more citing papers are in PubMed but not listed here.

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

10 authors at 5 institutions in 2 countries.

Yuki FunauchiLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Chizu TanikawaLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Paulisally Hau Yi LoLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Jinichi MoriLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Yataro DaigoCenter for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Atsushi TakanoCenter for Antibody and Vaccine Therapy, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Yohei MiyagiMolecular Pathology and Genetics Division, Kanagawa Cancer Center, Yokohama 241-0815, Japan.
Atsushi OkawaDepartment of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Yusuke NakamuraDepartments of Medicine and Surgery and Center for Personalized Therapeutics, The University of Chicago, USA.
Koichi MatsudaLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
The University of Tokyo · JPTokyo Medical and Dental University · JPUniversity of Tokyo Hospital · JPKanagawa Cancer CenterUniversity of Chicago · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulation of iron in tissues increases the risk of cancer, but iron regulatory mechanisms in cancer tissues are largely unknown. Here, we report that p53 regulates iron metabolism through the transcriptional regulation of ISCU (iron-sulfur cluster assembly enzyme), which encodes a scaffold protein that plays a critical role in Fe-S cluster biogenesis. p53 activation induced ISCU expression through binding to an intronic p53-binding site. Knockdown of ISCU enhanced the binding of iron regulatory protein 1 (IRP1), a cytosolic Fe-S protein, to an iron-responsive element in the 5' UTR of ferritin heavy polypeptide 1 (FTH1) mRNA and subsequently reduced the translation of FTH1, a major iron storage protein. In addition, in response to DNA damage, p53 induced FTH1 and suppressed transferrin receptor, which regulates iron entry into cells. HCT116 p53(+/+) cells were resistant to iron accumulation, but HCT116 p53(-/-) cells accumulated intracellular iron after DNA damage. Moreover, excess dietary iron caused significant elevation of serum iron levels in p53(-/-) mice. ISCU expression was decreased in the majority of human liver cancer tissues, and its reduced expression was significantly associated with p53 mutation. Our finding revealed a novel role of the p53-ISCU pathway in the maintenance of iron homeostasis in hepatocellular carcinogenesis.

Indexed as

HomeostasisSignal TransductionAnimalsCarcinoma, HepatocellularCell Line, TumorDNA DamageFerritinsGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockout TechniquesHumansIntracellular SpaceIronIron Regulatory Protein 1Iron-Sulfur ProteinsLiver NeoplasmsFerritinsFTH1 protein, humanIronIron Regulatory Protein 1Iron-Sulfur ProteinsISCU protein, humanOxidoreductasesRNA IsoformsTumor Suppressor Protein p53

Identifiers

PMID26560363
PMCPMC4642350
OpenAlexW2407541543

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LicenceCC BY
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Registered trials

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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.