Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Tumor immune evasion through IRGQ-directed autophagy

ABSTRACT: interactome of endogenous IRGQ during basal and autophagy-inducing conditions

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Lina Herhaus

LAB HEAD: Lina Herhaus

PROVIDER: PXD045117 | Pride | 2024-11-01

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	20200207_MHO_LH_mCh-IRGQ_01.raw	Raw
	20200207_MHO_LH_mCh-IRGQ_02.raw	Raw
	20200207_MHO_LH_mCh-IRGQ_03.raw	Raw
	20200207_MHO_LH_mCh-IRGQ_CCCP4h_01.raw	Raw
	20200207_MHO_LH_mCh-IRGQ_CCCP4h_02.raw	Raw

Items per page:

1 - 5 of 15

Publications

IRGQ-mediated autophagy in MHC class I quality control promotes tumor immune evasion.

Herhaus Lina L Gestal-Mato Uxía U Eapen Vinay V VV Mačinković Igor I Bailey Henry J HJ Prieto-Garcia Cristian C Misra Mohit M Jacomin Anne-Claire AC Ammanath Aparna Viswanathan AV Bagarić Ivan I Michaelis Jolina J Vollrath Joshua J Bhaskara Ramachandra M RM Bündgen Georg G Covarrubias-Pinto Adriana A Husnjak Koraljka K Zöller Jonathan J Gikandi Ajami A Ribičić Sara S Bopp Tobias T van der Heden van Noort Gerbrand J GJ Langer Julian D JD Weigert Andreas A Harper J Wade JW Mancias Joseph D JD Dikic Ivan I

Cell 20241030 25

The autophagy-lysosome system directs the degradation of a wide variety of cargo and is also involved in tumor progression. Here, we show that the immunity-related GTPase family Q protein (IRGQ), an uncharacterized protein to date, acts in the quality control of major histocompatibility complex class I (MHC class I) molecules. IRGQ directs misfolded MHC class I toward lysosomal degradation through its binding mode to GABARAPL2 and LC3B. In the absence of IRGQ, free MHC class I heavy chains do no ...[more]

PMID: 39481378

Similar Datasets

Tumor immune evasion mediated through IRGQ-directed autophagy

Project description:SurfaceOME of IRGQ WT and KO 8988T cells under basal conditions

2024-11-01 | PXD045259 | Pride

Tumor immune evasion through IRGQ-directed autophagy

Project 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.

2025-03-28 | PXD044618 | Pride

GABARAP-L2 WT, S87/88D or A interactomes

Project description:TBK1 phosphorylates GABARAP-L2 S87/88. In order to test if this phosphomimetic mutation in GABARAP-L2 changes its binding to other proteins a mass spectrometry based interactome study was performed.

2019-11-06 | PXD015155 | Pride

The autophagy receptor SQSTM1/p62 is a restriction factor of HCMV infection

Project description:Background: Intrinsic defence mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here we addressed the question how the autophagy receptor sequestome 1 (SQSTM1/p62, herein termed p62) interfered with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9- mediated genome editing, mass spectrometry and expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection. (3) Results: Knockout of p62 led to enhanced HCMV progeny release. Mass spectrometry revealed an interaction of p62 with cellular proteins required for nucleo-cytoplasmic transport. Phosphoproteomics further revealed that p62 is hyperphosphorylated at position S272 in HCMV-infected cells. Phosphorylated p62 showed enhanced nuclear retention, concordant with enhanced interaction with viral proteins relevant for genome replication and nuclear capsid egress. This modification led to reduced HCMV progeny release, compared to a unphosphorylated version of p62. (4) Conclusions: p62 is a restriction factor for HCMV replication The activity of the receptor appears to be regulated by phosphorylation at position S272, leading to enhanced nuclear localization, viral protein degradation and impairment of progeny production.

2025-05-13 | PXD055196 | Pride

The autophagy receptor SQSTM1/p62 is a restriction factor of HCMV infection

Project description:(1) Background: Intrinsic defence mechanisms are pivotal host strategies to restrict viruses already at early stages of their infection. Here we addressed the question how the autophagy receptor sequestome 1 (SQSTM1/p62, herein termed p62) interfered with human cytomegalovirus (HCMV) infection. (2) Methods: CRISPR/Cas9- mediated genome editing, mass spectrometry and expression of p62 phosphovariants from recombinant HCMVs were used to address the role of p62 during infection. (3) Results: Knockout of p62 led to enhanced HCMV progeny release. Mass spectrometry revealed an interaction of p62 with cellular proteins required for nucleo-cytoplasmic transport. Phosphoproteomics further revealed that p62 is hyperphosphorylated at position S272 in HCMV-infected cells. Phosphorylated p62 showed enhanced nuclear retention, concordant with enhanced interaction with viral proteins relevant for genome replication and nuclear capsid egress. This modification led to reduced HCMV progeny release, compared to a unphosphorylated version of p62. (4) Conclusions: p62 is a restriction factor for HCMV replication The activity of the receptor appears to be regulated by phosphorylation at position S272, leading to enhanced nuclear localization, viral protein degradation and impairment of progeny production.

2025-05-07 | PXD055194 | Pride

The autophagy receptor SQSTM1/p62 is a restriction factor of HCMV infection

2025-05-07 | PXD055195 | Pride

Versatile regulation of autophagy by the deubiquitinase USP11

Project description:Ubiquitination is a versatile post-translational modification known to regulate autophagy. Here, we show that loss of the deubiquitinase USP11 leads to an increase in the autophagic flux. To investigate the molecular details of how USP11 impacts autophagy, we determined interaction partners of USP11 using an affinity purification-mass spectrometry approach. GFP-tagged, catalytically inactive USP11(C318S) was overexpressed in 293 cells. After 4 hour treatment with Torin 1, an inhibitor of mTOR that induces autophagy, cells were lysed and samples further processed for analysis. Catalytically inactive USP11 was used to increase the chances of capturing both interaction partners and potential substrates. We identified many autophagy-related proteins that co-precipitated with USP11, suggesting that USP11 does not regulate autophagy via a single substrate, but that the observed phenotype is the sum of many interactions, each of which should be independently investigated in more detail. Our work focused on elucidating the regulation of autophagy via the lipid kinase complex PI3KC3 complex I, as one of its components (VPS15) was identified in our USP11 interactome data. PI3KC3 complex I is crucial for initiation of autophagosome formation at the endoplasmatic reticulum. USP11 knockout caused an increase in complex activity, which could explain enhanced autophagy in these cells.

2022-02-16 | PXD022143 | Pride

Autophagy content profiling in human cells

Project description:Identification of autophagy substrates by directing APEX2 to autophagosomes and immune isolation of lysosomes.

2021-01-27 | PXD020758 | Pride

HDX-MS analysis of IRGQ in the presence of GABARAP-L2 and LC3B

Project 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 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, free MHC-I heavy chains accumulate in the cell and additionally 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.

2024-11-26 | PXD045212 | Pride

Total porteome of liver tumors from mice (p53, MYC driven)

Project 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 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.

2024-10-31 | PXD044985 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data