PXD040862-1

PXD040862 is an original dataset announced via ProteomeXchange.

Title	MALT1 paracaspase controls cholesterol homeostasis in glioblastoma stem-like cells through lysosome proteome shaping
Description	Glioblastoma stem-like cells (GSCs) compose a tumor-initiating and propagating-population, remarkably vulnerable to any variation in the stability and integrity of the endolysomal compartment. Previous work showed that the expression and activity of the paracaspase MALT1 control GSC viability via lysosomal abundance. However, the underlying mechanisms remain elusive. By combining RNAseq to quantitative proteomic analysis, we now report that MALT1 inhibition in patient-derived GSCs causes severe defects in the homeostasis of cholesterol, which aberrantly accumulated in lysosomes. This failure in cholesterol supply culminates in cell death and autophagy defects, which can be partially reverted by providing exogenous membrane-permeable cholesterol to GSCs. From a molecular standpoint, targeted lysosome proteome analysis unraveled that NPC1/2 lysosomal cholesterol transporters were exhausted when MALT1 is held in check. Accordingly, we found that hindering NPC1 and NPC2 phenocopies MALT1 inhibition. This supports the notion that GSC fitness relies on lysosomal cholesterol homeostasis.
HostingRepository	PRIDE
AnnounceDate	2025-01-16
AnnouncementXML	Submission_2025-01-16_09:24:28.753.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johanna BRUCE
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-14 09:33:02	ID requested
⏵ 1	2025-01-16 09:24:29	announced

Maghe C, Trillet K, Andr, é, -Gr, é, goire G, Kerherv, é M, Merlet L, Jacobs KA, Schauer K, Bid, è, re N, Gavard J, The paracaspase MALT1 controls cholesterol homeostasis in glioblastoma stem-like cells through lysosome proteome shaping. Cell Rep, 43(1):113631(2024) [pubmed]

10.1016/j.celrep.2023.113631;

submitter keyword: MALT1, SREBP2, Niemann-Pick type C1, LysoIP,Glioblastoma, Lysosomes, Cholesterol

Gavard Julie
contact affiliation	Team SOAP, CRCI2NA, Nantes Université, Inserm, CNRS, Université d’Angers, Nantes, France
contact email	julie.gavard@inserm.fr
lab head
Johanna BRUCE
contact affiliation	Proteom’IC facility, Université Paris Cité, CNRS, INSERM, Institut Cochin, F-75014 PARIS
contact email	johanna.bruce@inserm.fr
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/2025/01/PXD040862

PRIDE project URI

• PRIDE
  1. PXD040862
     1. Label: PRIDE project
     2. Name: MALT1 paracaspase controls cholesterol homeostasis in glioblastoma stem-like cells through lysosome proteome shaping