PXD041821-2

PXD041821 is an original dataset announced via ProteomeXchange.

Title	Nuclear MTHFD2 secures centromere methylation, chromosome stability and correct mitosis progression
Description	Subcellular compartmentalization of metabolic enzymes may elicit specific cellular functions by establishing a unique metabolic environment. Indeed, the nuclear translocation of certain metabolic enzymes is required for epigenetic regulation and gene expression control. Here, we reveal that, in cancer cells, the mitochondrial enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) localizes in the nucleus during the G2-M phase of the cell cycle to secure mitosis progression. Nuclear MTHFD2 interacts with proteins involved in mitosis regulation and centromere stability, including the methyltransferases KMT5A and DNMT3B. Loss of MTHFD2 induces centromere overexpression and severe methylation defects, and impedes correct mitosis completion. As a consequence, MTHFD2 deficient cells accumulate chromosomal aberrations arising from chromosome congression and segregation defects. Blocking the catalytic nuclear function of MTHFD2 recapitulates the phenotype observed in MTHFD2 deficient cells, attributing to nuclear MTHFD2 an enzymatic active role in controlling mitosis. Our discovery uncovers a nuclear moonlighting role for the cancer target MTHFD2, and emphasizes that cancer metabolism rewiring may encompass the relocation of metabolic enzymes to alternative subcellular compartments.
HostingRepository	PRIDE
AnnounceDate	2024-12-02
AnnouncementXML	Submission_2024-12-02_03:22:21.581.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eva Borràs
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-26 02:52:25	ID requested
1	2024-11-28 05:27:12	announced
⏵ 2	2024-12-02 03:22:22	announced	2024-12-02: Updated project metadata.

10.1038/S41467-024-53877-Z;

Pardo-Lorente N, Gkanogiannis A, Cozzuto L, Ga, ñ, ez Zapater A, Espinar L, Ghose R, Severino J, Garc, í, a-L, ó, pez L, Aydin RG, Martin L, Neguembor MV, Darai E, Cosma MP, Batlle-Morera L, Ponomarenko J, Sdelci S, Nuclear localization of MTHFD2 is required for correct mitosis progression. Nat Commun, 15(1):9529(2024) [pubmed]

10.1038/s41467-024-51847-z;

submitter keyword: Folate metabolism, methylation, mitosis, centromere, cell cycle

Eduard Sabido
contact affiliation	CRG/UPF
contact email	eduard.sabido@crg.eu
lab head
Eva Borràs
contact affiliation	UPF
contact email	eva.borras@upf.edu
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/2024/11/PXD041821

PRIDE project URI

• PRIDE
  1. PXD041821
     1. Label: PRIDE project
     2. Name: Nuclear MTHFD2 secures centromere methylation, chromosome stability and correct mitosis progression