PXD057389-1

PXD057389 is an original dataset announced via ProteomeXchange.

Title	FBXW7 alleviates c-MYC repression of pyruvate carboxylase to support metabolic flexibility
Description	Metabolic flexibility, or the ability to adapt to environmental fluctuations, is key to the survival and growth of all living organisms. In mammals, the pathways supporting cell proliferation in nutrient-limiting conditions have not been fully elucidated, although cancers are known to display metabolic dependencies that can be targeted for therapy. Here, we combine systematic nutrient and genome-wide CRISPR/Cas9 screening to provide a comprehensive map of the signaling and metabolic pathways that support cell proliferation in glutamine-limited conditions. We focus on pyruvate anaplerosis and discover a mechanism by which the tumor suppressor FBXW7 controls a MYC-dependent cluster of epigenetic repressors that bind the pyruvate carboxylase (PC) promoter, leading to histone deacetylation, reduced PC expression and glutamine addiction. Our work sheds light on the molecular mechanisms that support metabolic flexibility, and on the nutrients and pathways involved in glutamine dependency, a hallmark of several cancers.
HostingRepository	PRIDE
AnnounceDate	2026-01-30
AnnouncementXML	Submission_2026-01-30_10:07:40.082.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	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-31 04:02:40	ID requested
⏵ 1	2026-01-30 10:07:40	announced

Dataset with its publication pending

submitter keyword: pyruvate carboxylation, PC, FBXW7,glutamine dependency, nutrient-genetic screens

Alexis A. Jourdain
contact affiliation	Department of Immunobiology, University of Lausanne (Chemin des Boveresses 155, Epalinges 1066)
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. PXD057389
     1. Label: PRIDE project
     2. Name: FBXW7 alleviates c-MYC repression of pyruvate carboxylase to support metabolic flexibility