Evidence map›Paper›PMID 41196952›Full record

ArticleScience (New York, N.Y.)2025

A non-enzymatic role of Nudix hydrolase 5 in repressing purine de novo synthesis.

Tuan-Anh Nguyen, Jung-Ming G Lin, Anne-Sophie M C Marques, Maximilian Fottner, Ludwig G Bauer, Andreas Reicher, Diana Daum, Lorenzo Scrofani, Yusi Liu, Carol Cheng and 34 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Review
  2. Review
  3. Exploring potential biomarkers of diffuse large B-cell lymphoma through multi-dimensional data.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
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

44 authors.

Tuan-Anh Nguyen *CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0001-7809-5175
Jung-Ming G Lin *CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-3260-5544
Anne-Sophie M C Marques *Centre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK.ORCID 0009-0005-5726-508X
Maximilian FottnerLaboratory for Organic Chemistry (LOC), Department of Chemistry and Applied Biosciences (D-CHAB), ETH Zurich, Zurich, Switzerland.ORCID 0000-0002-8628-183X
Ludwig G BauerCentre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK.ORCID 0000-0002-2235-3945
Andreas ReicherCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Diana DaumCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0009-0007-3827-4970
Lorenzo ScrofaniCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0009-0000-6805-8338
Yusi LiuCentre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK.
Carol ChengCentre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK.ORCID 0009-0006-3165-5183
Luna D'Angelo L D DCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0009-0005-6268-3462
Juan SanchezCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-5920-7618
Christoph BueschlCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-1729-9785
Nara MarellaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0001-5254-6089
Pisanu BuphamalaiCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Florian TraversiDivision of Metabolism and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.
Maša BerešInstitute of Pharmacology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.ORCID 0009-0008-5247-5880
Herwig P MollInstitute of Pharmacology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-6438-9068
Marton SiklosCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Jakob-Wendelin GengerCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-4502-1094
Gerald HofstaetterCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0009-0009-4111-1763
Ludovica VillantiCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Monika MalikCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Christoph KlimekCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Kathrin RunggatscherCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Bettina GuertlCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Jesper S HansenCentre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK.
Sarah DobnerCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0009-0000-4186-9958
Olga BabosovaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0001-7036-6807
Tina BecirovicCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0009-0009-6074-2907
Laura P M H de RooijCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-1810-4620
Emilio CasanovaInstitute of Pharmacology, Center of Physiology and Pharmacology & Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-7992-5361
Anna KorenCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
D Sean FroeseDivision of Metabolism and Children's Research Center, University Children's Hospital, University of Zurich, Zurich, Switzerland.ORCID 0000-0003-1557-3517
David S RosenblattDepartment of Human Genetics, McGill University, Montreal, Canada.ORCID 0000-0002-0548-365X
Kristaps KlavinsCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Andreas BergthalerCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-0597-1976
Jörg MencheCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-1583-6404
J Thomas HannichCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0002-2286-4956
Miriam AbeleCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-0084-2999
Sara SdelciCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-1330-4364
Kathrin LangLaboratory for Organic Chemistry (LOC), Department of Chemistry and Applied Biosciences (D-CHAB), ETH Zurich, Zurich, Switzerland.ORCID 0000-0002-1318-6567
Kilian V M HuberCentre for Medicines Discovery, Nuffield Department of Medicine, Oxford, UK.ORCID 0000-0002-1103-5300
Stefan KubicekCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.ORCID 0000-0003-0855-8343

Funding

European Research Council 772437Swiss National Science Foundation 192505
6 · The paper itself

Abstract

Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. By investigating chemical and genetic dependencies caused by mutations in methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1), we discovered a key role for Nudix hydrolase 5 (NUDT5) in regulating purine de novo synthesis. Genetic depletion and selective chemical degradation showed that a scaffolding role, rather than NUDT5 enzymatic activity, was causing this phenotype. NUDT5 interacted with phosphoribosyl pyrophosphate amidotransferase (PPAT), the rate-limiting enzyme of purine de novo synthesis, to repress the pathway in response to increased purine abundance. Through this mechanism, loss of NUDT5 mediates resistance to purine analogs in cancer treatment and prevents adenosine toxicity in MTHFD1 deficiency.

Indexed as

Nudix HydrolasesPurinesPyrophosphatasesAmidophosphoribosyltransferaseFolic AcidFormate-Tetrahydrofolate LigaseHumansMethenyltetrahydrofolate CyclohydrolaseMethylenetetrahydrofolate Dehydrogenase (NADP)Minor Histocompatibility AntigensMutationAmidophosphoribosyltransferaseFolic AcidFormate-Tetrahydrofolate LigaseMethenyltetrahydrofolate CyclohydrolaseMethylenetetrahydrofolate Dehydrogenase (NADP)Minor Histocompatibility AntigensMTHFD1 protein, humanNudix HydrolasesNUDT5 protein, humanpurinePurinesPyrophosphatases

Identifiers

PMID41196952
PMCPMC7618541

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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.