PXD044618

PXD044618 is an original dataset announced via ProteomeXchange.

Title	Tumor immune evasion through IRGQ-directed autophagy
Description	The 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 GABARAP-L2 and LC3B. IRGQ specifically recognizes 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 T cell immune responses. Accordingly, mice suffering from hepatocellular carcinoma with reduced IRGQ levels display higher survival rates and bear more activated CD8+ T cells. Conversly, 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 towards tumorigenic IRGQ knock-out cells. Thus, we identify IRGQ as a regulator of MHC-I quality control, mediating tumor immune evasion and marking it as a potential biomarker and therapeutic target.
HostingRepository	PRIDE
AnnounceDate	2025-03-28
AnnouncementXML	Submission_2025-03-28_05:40:15.126.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joao Paulo
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-18 05:14:07	ID requested
⏵ 1	2025-03-28 05:40:15	announced

Dataset with its publication pending

submitter keyword: LC3B, autophagy, immune evasion, hepatocellular carcinoma, IRGQ, GABARAP-L2,MHC class I

Joseph D. Mancias
contact affiliation	Department of Radiation Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston MA 02215
contact email	joseph_mancias@dfci.harvard.edu
lab head
Joao Paulo
contact affiliation	Harvard Medical School
contact email	joao_paulo@post.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044618
     1. Label: PRIDE project
     2. Name: Tumor immune evasion through IRGQ-directed autophagy