PXD050014-2

PXD050014 is an original dataset announced via ProteomeXchange.

Title	O-GlcNAcylation of FOXK1 orchestrates the E2F pathway
Description	Gene transcription is a highly regulated process, and deregulation of transcription factors activity underlie numerous pathologies including cancer. FOXK1 and FOXK2 (FOXK1/2) transcription factors have recently emerged as important regulators of cell metabolism, autophagy and cell differentiation. While FOXK1/2 possesses many overlapping functions in normal biology, their specific functions as well as deregulation of their transcriptional activity in cancer is less clear and often contradictory. FOXK1, but less FOXK2, is known to have oncogenic properties as higher expression levels of FOXK1 has been observed in several cancers and is correlated with tumor progression, invasion, and metastasis. However, the molecular mechanism by which FOXK1 exert its oncogenic properties in caner remains unknown. Here we show that elevated expression of FOXK1, but not FOXK2, in normal human fibroblasts promotes transcription of E2F target genes associated with increased proliferation and delayed senescence entry. Fibroblasts overexpressing FOXK1 are also more prone to cellular transformation with minimal oncogenic combinations, suggesting important oncogenic proprieties of FOXK1. Mechanistically, we found that FOXK1, but not FOXK2, is specifically modified by O-GlcNAcylation. FOXK1 O-GlcNAcylation is modulated during the cell cycle and its highest levels coincides with the G1/S phase transition. Moreover, FOXK1 O-GlcNAcylation is increased following cell transformation and loss of this modification leads to decreased FOXK1 ability to promote cellular transformation and tumor growth. Cells overexpressing FOXK1 O-GlcNAcylation-defective mutants have lower E2F1 expression, cell proliferation, and tumour growth. Our results define a distinct role of FOXK1 via O-GlcNAcylation in controlling the cell cycle through the orchestration of the E2F pathway.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:44:24.828.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD050014
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; complex glycosylation; deamidated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-21 12:52:56	ID requested
1	2024-06-10 13:32:31	announced
⏵ 2	2024-10-22 06:44:25	announced	2024-10-22: Updated project metadata.

10.6019/PXD050014;

Masclef L, Ahmed O, Iannantuono N, Gagnon J, Gushul-Leclaire M, Boulay K, Estavoyer B, Echbicheb M, Poy M, Boubacar KA, Boubekeur A, Menggad S, Schcolnik-Cabrera A, Balsalobre A, Bonneil E, Thibault P, Hulea L, Tanaka Y, Antoine-Mallette F, Drouin J, Affar EB, O-GlcNAcylation of FOXK1 orchestrates the E2F pathway and promotes oncogenesis. bioRxiv, ():(2024) [pubmed]

10.1101/2024.03.01.582838;

submitter keyword: E2F pathway, O-GlcNAcylation,FOXK1

Bachir El Affar
contact affiliation	Centre de recherche hopital Maisonneuve Rosemont
contact email	el.affar.bachir@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050014
     1. Label: PRIDE project
     2. Name: O-GlcNAcylation of FOXK1 orchestrates the E2F pathway