PXD067706-1

PXD067706 is an original dataset announced via ProteomeXchange.

Title	Large-scale interaction proteomic profiling of NUDT5 and PPAT interactors
Description	Folate metabolism is intricately linked to purine de novo synthesis through the incorporation of folate-derived one-carbon units into the purine scaffold. Here, we investigate the chemical and genetic dependencies caused by mutations in the folate enzyme MTHFD1 and discover a key role for Nudix hydrolase 5 (NUDT5) in regulating purine de novo synthesis. Through genetic knockout and development of a selective chemical NUDT5 degrader, we uncover an unprecedented scaffolding role rather than NUDT5 enzymatic activity is responsible for this phenotype. We find that NUDT5 interacts with the rate-limiting enzyme of purine de novo synthesis, PPAT, to repress the pathway in response to elevated purine levels. Our findings establish NUDT5 as an important regulator of purine de novo synthesis and elucidate its role in mediating sensitivities to purine analogs in cancer treatment and to adenosine in MTHFD1 deficiency.
HostingRepository	PRIDE
AnnounceDate	2025-11-03
AnnouncementXML	Submission_2025-11-03_14:08:38.962.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ludwig Bauer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-25 14:22:30	ID requested
⏵ 1	2025-11-03 14:08:39	announced

Dataset with its publication pending

submitter keyword: interaction proteomics

Kilian Huber
contact affiliation	Centre for Medicines Discovery, Nuffield Department of Medicine; Oxford OX3 7BN, UK. Target Discovery Institute, Nuffield Department of Medicine; Oxford OX3 7BN, UK.
contact email	kilian.huber@cmd.ox.ac.uk
lab head
Ludwig Bauer
contact affiliation	University of Oxford
contact email	ludwig.bauer@st-hughs.ox.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/11/PXD067706

PRIDE project URI

• PRIDE
  1. PXD067706
     1. Label: PRIDE project
     2. Name: Large-scale interaction proteomic profiling of NUDT5 and PPAT interactors