PXD034141-1

PXD034141 is an original dataset announced via ProteomeXchange.

Title	FOXA2 controls the anti-oxidant response in FH-deficient cells independent of NRF2
Description	Hereditary Leiomyomatosis and renal cell cancer (HLRCC) is caused by germline mutations of fumarate hydratase (FH) and subsequence accumulation of fumarate. Fumarate is known to activate the anti-oxidant response by KEAP1 succination and nuclear translocation of the transcription factor NRF2. The activation of the anti-oxidant response and is key for cellular survival in FH-deficient cells. To explore the global effects of FH loss and fumarate on the chromatin landscape, we performed unbiased multi-omic analyses. By integrating chromatin accessibility and histone ChIP-seq profiles, we identify additional transcription factor networks involved in the highly remodelled chromatin landscape of FH-deficient cells. Here, we implicate FOXA2 in the maintenance of FH-deficient cells by directly regulating anti-oxidant response genes and subsequent metabolic output. We also find that FOXA2 regulates anti-oxidant genes independent of the canonical anti-oxidant regulator NRF2. The identification of FOXA2 as an anti-oxidant regulator provide new insights into the molecular mechanisms behind cell responses to fumarate accumulation, and potentially provide new avenues for therapeutic intervention for HLRCC.
HostingRepository	PRIDE
AnnounceDate	2026-07-20
AnnouncementXML	Submission_2026-07-19_16:34:40.823.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joshua Kent
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; deaminated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-26 01:24:55	ID requested
⏵ 1	2026-07-19 16:34:42	announced

10.1016/j.celrep.2023.112751;

Rogerson C, Sciacovelli M, Maddalena LA, Pouikli A, Segarra-Mondejar M, Valcarcel-Jimenez L, Schmidt C, Yang M, Ivanova E, Kent J, Mora A, Cheeseman D, Carroll JS, Kelsey G, Frezza C, FOXA2 controls the anti-oxidant response in FH-deficient cells. Cell Rep, 42(7):112751(2023) [pubmed]

submitter keyword: anti-oxidant response, NRF2, fumarate hydratase,FOXA2

Christian Frezza
contact affiliation	MRC Cancer Unit, University of Cambridge, Hutchison MRC Research Centre, Cambridge, Biomedical Campus, Cambridge, United Kingdom. CECAD Research Center, Faculty of Medicine, University Hospital Cologne, Cologne, Germany.
contact email	christian.frezza@uni-koeln.de
lab head
Joshua Kent
contact affiliation	The University of Cambridge
contact email	joshua.kent@cruk.cam.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034141
     1. Label: PRIDE project
     2. Name: FOXA2 controls the anti-oxidant response in FH-deficient cells independent of NRF2