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PXD044985

PXD044985 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleTotal porteome of liver tumors from mice (p53, MYC driven)
DescriptionThe autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumor progression. Here we show that immunity-related GTPase family Q protein (IRGQ) acts in the quality control of MHC-I molecules and directs misfolded MHC-I for lysosomal degradation through its binding to GABARAPL2 and LC3B. IRGQ specifically targets the non-conformational heavy chains of MHC-I, sorting them for degradation through the autophagy-lysosome system. In the absence of IRGQ, MHC-I heavy chains accumulate in the cell and partly get localized to the cell surface, thereby increasing interactions with mature MHC-I molecules and promoting immune response. Accordingly, mice suffering from hepatocellular carcinoma with reduced IRGQ levels display higher survival rates and bear more activated CD8+ T cells. Similarly, low IRGQ expression in human liver cancer correlates with higher levels of MHC-I molecules in the tumors, and patient survival is directly affected by IRGQ expression levels in CD8+ enriched tumors. Moreover, human T cells are more reactive toward tumorigenic IRGQ knock-out cells. Thus, we reveal IRGQ as a regulator of MHC-I quality control, mediating tumor immune evasion and marking it as a potential biomarker and therapeutic target.
HostingRepositoryPRIDE
AnnounceDate2024-10-31
AnnouncementXMLSubmission_2024-10-31_06:06:36.460.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterUxia Gestal Mato
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-31 00:14:42ID requested
12024-10-31 06:06:36announced
Publication List
10.1016/J.CELL.2024.09.048;
Keyword List
submitter keyword: TMT,Liver, MYC, Mice, p53
Contact List
Lina Herhaus
contact affiliationInstitute of Biochemistry II Goethe University Medical School University Hospital, Bldg 75 Theodor-Stern-Kai 7 60590 Frankfurt am Main Germany
contact emailherhaus@em.uni-frankfurt.de
lab head
Uxia Gestal Mato
contact affiliationInstitut für Biochemie II - Goethe Universität Frankfurt
contact emailgestalmato@em.uni-frankfurt.de
dataset submitter
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Dataset FTP location
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