PXD053800

PXD053800 is an original dataset announced via ProteomeXchange.

Title	Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation
Description	The CEBPA transcription factor is frequently mutated in acute myeloid leukemia (AML). Mutations in the CEBPA gene, which are typically biallelic, result in the production of a shorter isoform known as p30. Both the canonical 42-kDa isoform (p42) and the AML-associated p30 isoform bind chromatin and activate transcription, but the specific transcriptional programs controlled by each protein and how they are linked to a selective advantage in AML is not well understood. Here, we show that cells expressing the AML-associated p30 have reduced baseline inflammatory gene expression and display altered dynamics of transcriptional induction in response to LPS, consequently impacting cytokine secretion. This confers p30-expressing cells an increased resistance to the adverse effects of prolonged exposure to inflammatory signals. Mechanistically, we show that these differences primarily result from the differential regulation of AP-1 family proteins. In addition, we find that the altered function of the AP-1 member ATF4 in p30-expressing cells alters their response to ER stress. Collectively, these findings uncover a novel link between mutant CEBPA, inflammation and the stress response, potentially revealing a new vulnerability in AML.
HostingRepository	PRIDE
AnnounceDate	2025-03-13
AnnouncementXML	Submission_2025-03-13_03:21:21.153.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felix Weiss
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-09 07:48:18	ID requested
⏵ 1	2025-03-13 03:21:21	announced

Dataset with its publication pending

submitter keyword: cancer,Transcription, inflammation

Felix Meissner
contact affiliation	Institute of Innate Immunity, Department for Systems Immunology and Proteomics, University Hospital Bonn, University of Bonn, 53127 Bonn, Germany
contact email	felix.meissner@uni-bonn.de
lab head
Felix Weiss
contact affiliation	University Hospital Bonn
contact email	fweiss@uni-bonn.de
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/2025/03/PXD053800

PRIDE project URI

• PRIDE
  1. PXD053800
     1. Label: PRIDE project
     2. Name: Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation