PXD060320-1

PXD060320 is an original dataset announced via ProteomeXchange.

Title	NUDT5 restrains PPAT to promote pyrimidine synthesis and effective nucleobase therapy - sgNUDT5 proteomics
Description	Nucleotides are essential building blocks for nucleic acid synthesis, signaling, and metabolism. Rapidly proliferating cells require large amounts of nucleotides, making nucleotide metabolism a widely exploited target for cancer therapy. However, resistance frequently emerges, highlighting the need for a deeper understanding of nucleotide regulation. Here, we use uridine-sensitized CRISPR-Cas9 screening to reveal novel regulators of pyrimidine synthesis. We identify NUDT5 which we show binds to and negatively regulates PPAT, the rate-limiting enzyme in purine biosynthesis. We demonstrate the NUDT5-PPAT interaction prevents excessive purine production, maintains phosphoribosyl pyrophosphate (PRPP), a critical substrate for pyrimidine synthesis, and thus enhances conversion of nucleobase analogs into active anti-cancer molecules. We further report that NUDT5 regulates PPAT independently of its enzymatic activity and can be displaced by PRPP, revealing intricate allosteric regulation. Our findings reveal a previously unrecognized mechanism for maintaining nucleotide balance and positions NUDT5 as a potential therapeutic target for overcoming resistance to chemotherapy in proliferative diseases.
HostingRepository	PRIDE
AnnounceDate	2025-10-29
AnnouncementXML	Submission_2025-10-29_05:08:52.331.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexis Jourdain
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-29 07:10:20	ID requested
⏵ 1	2025-10-29 05:08:52	announced

Dataset with its publication pending

submitter keyword: CRISPR screen, demethoxy-coenyzme Q, NUDT5,Pyrimidine, purine

Alexis Jourdain
contact affiliation	Dpt. of Immunobiology, University of Lausanne, Chemin de Boveresses 155, 1066 Epalinges, Switzerland
contact email	alexis.jourdain@unil.ch
lab head
Alexis Jourdain
contact affiliation	Department of Immunobiology, University of Lausanne
contact email	alexis.jourdain@unil.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD060320
     1. Label: PRIDE project
     2. Name: NUDT5 restrains PPAT to promote pyrimidine synthesis and effective nucleobase therapy - sgNUDT5 proteomics