PXD041817

PXD041817 is an original dataset announced via ProteomeXchange.

Title	IRF2BP2 counteracts the ATF7/JDP2 heterodimer to prevent inflammatory overactivation in AML cells
Description	Acute myeloid leukemia (AML) is a hematological malignancy characterized by the abnormal proliferation and accumulation of immature myeloid cells in the bone marrow. Inflammation plays a crucial role in AML progression, but excessive activation of inflammatory pathways can also trigger cell death. IRF2BP2 is a chromatin regulator that has been implicated in AML pathogenesis, although its precise role in this disease is not fully understood. In this study, we demonstrate that in AML cells IRF2BP2 interacts with the transcriptional heterodimer ATF7/JDP2, which is involved to activate inflammatory pathways in AML cells. We show that IRF2BP2 is recruited by the ATF7/JDP2 dimer to chromatin and counteracts its gene activating function. Loss of IRF2BP2 leads to the overactivation of inflammatory pathways, resulting in immediate cell death. Our findings suggest that a delicate balance of activating and repressive transcriptional mechanisms establishes a pro-oncogenic inflammatory set-up in AML cells, and that manipulation of the ATF7/JDP2-IRF2BP2 regulatory axis may offer a potential vulnerability for AML treatment. Thus, our study provides new insights into the molecular mechanisms underlying AML pathogenesis and identifies a potential therapeutic target for AML treatment.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:39:29.075.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ignasi Forne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-26 00:15:45	ID requested
1	2024-05-16 00:30:43	announced
⏵ 2	2024-10-22 06:39:29	announced	2024-10-22: Updated project metadata.

10.1093/NAR/GKAE437;

submitter keyword: Interferon, ATF7, Transcriptional Regulation,IRF2BP2, JDP2, Inflammation, AML

Dr. Robert Liefke
contact affiliation	Institute of Molecular Biology and Tumor Research (IMT)Philipps University of Marburg, Marburg, 35043, Germany and Department of Hematology, Oncology, and Immunology, University Hospital Giessen and Marburg, Marburg, 35043, Germany
contact email	robert.liefke@imt.uni-marburg.de
lab head
Ignasi Forne
contact affiliation	Biomedical Center-LMU
contact email	ignasi.forne@lrz.uni-muenchen.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/2024/05/PXD041817

PRIDE project URI

• PRIDE
  1. PXD041817
     1. Label: PRIDE project
     2. Name: IRF2BP2 counteracts the ATF7/JDP2 heterodimer to prevent inflammatory overactivation in AML cells