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PXD047745-2

PXD047745 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTargeting NLRP3 inhibits AML progression by inducing PERK/eIF2-mediated apoptosis
DescriptionHyperactivation 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_06:55:01.052.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVeronika Schäpertöns
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-12-12 04:14:19ID requested
12024-08-14 08:01:45announced
22024-10-22 06:55:01announced2024-10-22: Updated project metadata.
Publication List
10.1186/S12964-024-01777-6;
Keyword List
submitter keyword: acute (myeloid) leukemia
Contact List
Dr. Constantin
contact affiliationDepartment of Biosciences, University of Salzburg
contact emailC.Blochl@lumc.nl
lab head
Veronika Schäpertöns
contact affiliationPLUS University of Salzburg
contact emailveronika.schaepertoens@protonmail.com
dataset submitter
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Dataset FTP location
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