PXD047745-2

PXD047745 is an original dataset announced via ProteomeXchange.

Title	Targeting NLRP3 inhibits AML progression by inducing PERK/eIF2-mediated apoptosis
Description	Hyperactivation of the NLRP3 inflammasome has been linked to disease progression in acute myeloid leukemia (AML). However, the precise mechanisms behind this pathology remain elusive. Here, we highlight not only a significant correlation between elevated NLRP3 expression and diminished overall survival in AML patients, but also a potential pathomechanism. We show that genetic deletion and pharmacological inhibition of NLRP3 leads to a reduction in AML cell survival by triggering apoptosis. Additionally, our proteomic analyses revealed NLRP3-dependent alterations in protein translation, substantiated by increased eIF2α phosphorylation in NLRP3-deficient AML cells. Furthermore, we show that inhibition of the eIF2α kinase PERK mitigates eIF2α phosphorylation and decreases apoptosis by reducing the expression of pro-apoptotic Bcl-2 family members to levels comparable to those of wild-type cells. Substantiating these observations, we found that deleting NLRP3 in engrafted AML cells led to reduced splenomegaly and AML cell infiltration into organs in mice. Taken together, our findings demonstrate that blocking NLRP3 induces apoptosis via PERK/eIF2, revealing a promising avenue for therapeutic intervention in AML.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:55:01.052.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Veronika Schäpertöns
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-12 04:14:19	ID requested
1	2024-08-14 08:01:45	announced
⏵ 2	2024-10-22 06:55:01	announced	2024-10-22: Updated project metadata.

10.1186/S12964-024-01777-6;

submitter keyword: acute (myeloid) leukemia

Dr. Constantin
contact affiliation	Department of Biosciences, University of Salzburg
contact email	C.Blochl@lumc.nl
lab head
Veronika Schäpertöns
contact affiliation	PLUS University of Salzburg
contact email	veronika.schaepertoens@protonmail.com
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/2024/08/PXD047745

PRIDE project URI

• PRIDE
  1. PXD047745
     1. Label: PRIDE project
     2. Name: Targeting NLRP3 inhibits AML progression by inducing PERK/eIF2-mediated apoptosis