PXD040500-1

PXD040500 is an original dataset announced via ProteomeXchange.

Title	KRAB zinc finger proteins ZNF587/ZNF417 protect lymphoma cells from replicative stress-induced inflammation
Description	The role of Krüppel-associated box zinc finger proteins (KZFPs), the largest family of repressive transcription factors (TFs) of the human genome, in the pathogenesis of diffuse large B cell lymphoma has not been addressed so far. By correlating the expression of KZFPs with patient outcome, we delineated a subset of 18 co-expressed KZFPs associated to poor prognosis, higher copy number alterations (CNA), and the suppression of hallmarks gene sets linked to immune rejection. Among them, the depletion of the ZNF587-ZNF417 pair of TF paralogs drastically impaired the proliferation of both activated B cell (ABC) and germinal center B (GCB) DLBCL cell lines, by triggering replicative stress through the awakening of dormant replication origins and profound alterations of the heterochromatin landscape. ZNF587/417 knockdown profoundly altered the transcriptomic landscape of U2932 (ABC) and OCI-Ly7 (GCB) cells, rewiring gene expression networks associated with good prognosis and upregulating interferon (IFN)/inflammatory-related genes through activation of the cGAS-STING DNA sensing pathway. These cells showed signs of altered immunogenicity with an enhanced MHC class I surface expression and a reshuffling of their immunopeptidome. Our study provides evidence that the ZNF587-ZNF417 paralog pair may promote lymphoma growth, the acquisition of genetic diversity, and its immune evasion by preventing excessive replicative stress. This suggests that these TFs participate in the epigenetic memory of lymphoma cells, thus highlighting the critical role of constitutive heterochromatin in maintaining the identity of poor-prognosis DLBCL.
HostingRepository	PRIDE
AnnounceDate	2024-03-15
AnnouncementXML	Submission_2024-03-15_03:33:20.760.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Michal Bassani-Sternberg
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-28 07:07:33	ID requested
⏵ 1	2024-03-15 03:33:21	announced
2	2024-10-22 06:33:33	announced	2024-10-22: Updated project metadata.

10.1158/0008-5472.can-23-1237;

Martins F, Rosspopoff O, Carlevaro-Fita J, Forey R, Offner S, Planet E, Pulver C, Pak H, Huber F, Michaux J, Bassani-Sternberg M, Turelli P, Trono D, A Cluster of Evolutionarily Recent KRAB Zinc Finger Proteins Protects Cancer Cells from Replicative Stress-Induced Inflammation. Cancer Res, 84(6):808-826(2024) [pubmed]

submitter keyword: diffuse large B cell lymphoma,Human zinc finger proteins, immunopeptidomics, ZNF587/417 knockdown

Michal Bassani-Sternberg
contact affiliation	Department of oncology UNIL CHUV Ludwig Institute for Cancer Research Lausanne Office B25A/04/94 Rue du Bugnon 25a, CH-1005 Lausanne
contact email	michal.bassani@chuv.ch
lab head
Michal Bassani-Sternberg
contact affiliation	UNIL/CHUV
contact email	michal.bassani@chuv.ch
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/2024/03/PXD040500

PRIDE project URI

• PRIDE
  1. PXD040500
     1. Label: PRIDE project
     2. Name: KRAB zinc finger proteins ZNF587/ZNF417 protect lymphoma cells from replicative stress-induced inflammation