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): Q Exactive HF

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

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

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

Charecterization of RBM42 interacting proteins in HCT116 cells with and without DNA damage

Project description:RNA binding motif protein 42 (RBM42) is an understudied gene mapped to 19q13.12 region and codes for a protein that consists of 480 amino acids, containing one RNA recognition motif (RRM) at its C-terminal region. We mapped the RBM42 interactome using ascorbate peroxidase (APEX2)-based proximity labelling combined with mass spectrometry. We utilized CRISPR-Cas9 methodology for biallelic knock-in APEX2 at the C-terminus of the endogenous RBM42 coding sequence (CDS) and established an HCT116 cell line expressing RBM42-APEX2 fusion. RBM42 interactome mapping was performed by using Control and and HCT116 expressing RBM42-APEX2 cells that were treated with DMSO or Etoposide (VP-16) that induce DNA repair and incubated in media containing biotin phenol, followed by H2O2 treatment, to activate APEX2 peroxidase activity. Pathway enrichment analysis revealed that the majority of proteins that appeared in proximity to RBM42 are implicated in mRNA splicing and processing. Furthermore, we observed a significant enrichment of proteins involved in cell cycle checkpoints and regulation, further highlighting the role of RBM42 in DNA damage response. Together, RBM42 interactome analysis substantiates its function as a splicing regulator and implicates it in additional cellular pathways related to mRNA metabolism and DNA damage response.

2023-11-22 | PXD034854 | Pride

Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.

Project description:Immune evasion is a major obstacle for cancer treatment. Common mechanisms of evasion include impaired antigen presentation caused by mutations or loss of heterozygosity of the major histocompatibility complex class I (MHC-I), which has been implicated in resistance to immune checkpoint blockade (ICB) therapy1-3. However, in pancreatic ductal adenocarcinoma (PDAC), which is resistant to most therapies including ICB4, mutations that cause loss of MHC-I are rarely found5 despite the frequent downregulation of MHC-I expression6-8. Here we show that, in PDAC, MHC-I molecules are selectively targeted for lysosomal degradation by an autophagy-dependent mechanism that involves the autophagy cargo receptor NBR1. PDAC cells display reduced expression of MHC-I at the cell surface and instead demonstrate predominant localization within autophagosomes and lysosomes. Notably, inhibition of autophagy restores surface levels of MHC-I and leads to improved antigen presentation, enhanced anti-tumour T cell responses and reduced tumour growth in syngeneic host mice. Accordingly, the anti-tumour effects of autophagy inhibition are reversed by depleting CD8+ T cells or reducing surface expression of MHC-I. Inhibition of autophagy, either genetically or pharmacologically with chloroquine, synergizes with dual ICB therapy (anti-PD1 and anti-CTLA4 antibodies), and leads to an enhanced anti-tumour immune response. Our findings demonstrate a role for enhanced autophagy or lysosome function in immune evasion by selective targeting of MHC-I molecules for degradation, and provide a rationale for the combination of autophagy inhibition and dual ICB therapy as a therapeutic strategy against PDAC.

| S-EPMC7296553 | biostudies-literature

Japanese encephalitis virus activates autophagy as a viral immune evasion strategy.

Project description:In addition to manipulating cellular homeostasis and survivability, autophagy also plays a crucial role in numerous viral infections. In this study, we discover that Japanese encephalitis virus (JEV) infection results in the accumulation of microtubule-associated protein 1 light chain 3-II (LC3-II) protein and GFP-LC3 puncta in vitro and an increase in autophagosomes/autolysosomes in vivo. The fusion between autophagosomes and lysosomes is essential for virus replication. Knockdown of autophagy-related genes reduced JEV replication in vitro, as indicated by viral RNA and protein levels. We also note that JEV infection in autophagy-impaired cells displayed active caspases cleavage and cell death. Moreover, we find that JEV induces higher type I interferon (IFN) activation in cells deficient in autophagy-related genes as the cells exhibited increased phosphorylation and dimerization of interferon regulatory factor 3 (IRF3) and mitochondrial antiviral signaling protein (MAVS) aggregation. Finally, we find that autophagy is indispensable for efficient JEV replication even in an IFN-defective background. Overall, our studies provide the first description of the mechanism of the autophagic innate immune signaling pathway during JEV infection.

| S-EPMC3540057 | biostudies-literature

Gene regulation in autophagy and apoptosis juncture

Project description:Autophagy to apoptosis switching event is an unexplored area. We were interested to explore the gene expression profile at this juncture. Our Microarray data emphasized that among all eNOS and p62 genes were markedly induced. In fuctional level eNOS expression activates mTORC1 followed by inhibition of autophagy. This ultimately allowed accumulation of p62 . Intraccellular accumulation of p62 sequestered unfolded toxic protein aggregates in mitochondria and ER resulting in to impaired redox regulation. Intraccelular ROS generation further sensitized cells for apoptosis and tilted autophagic response to apoptosis. Cells were treated with Tunicamycin as an inducer of both autophagy and apoptosis. At early stage of Tunicamycin treatment 24h , prostate cancer cell PC3 showed activation of autophagic process where apoptosis was not evident. Sustained ER stress with Tunicamycin induced late apoptoisis at 72h of treatment. Hence we isolated total RNA from Untreated cells, cells with Tunicamycin treatment after 24h and 72h. Further the RNA were used to perform whole genome microarray to analyze the gene expression profile at autophagy and apoptosis juncture. The selected genes were also validated by qPCR and western bot. Morover RNAi study were implemented to evaluate the signaling crosstalk at the juncture of autophagy and apoptosis.

2014-05-22 | E-GEOD-38643 | biostudies-arrayexpress

Midbody accumulation through evasion of autophagy contributes to cellular reprogramming and tumorigenicity.

Project description:The midbody is a singular organelle formed between daughter cells during cytokinesis and required for their final separation. Midbodies persist in cells long after division as midbody derivatives (MB(d)s), but their fate is unclear. Here we show that MB(d)s are inherited asymmetrically by the daughter cell with the older centrosome. They selectively accumulate in stem cells, induced pluripotent stem cells and potential cancer 'stem cells' in vivo and in vitro. MB(d) loss accompanies stem-cell differentiation, and involves autophagic degradation mediated by binding of the autophagic receptor NBR1 to the midbody protein CEP55. Differentiating cells and normal dividing cells do not accumulate MB(d)s and possess high autophagic activity. Stem cells and cancer cells accumulate MB(d)s by evading autophagosome encapsulation and exhibit low autophagic activity. MB(d) enrichment enhances reprogramming to induced pluripotent stem cells and increases the in vitro tumorigenicity of cancer cells. These results indicate unexpected roles for MB(d)s in stem cells and cancer 'stem cells'.

| S-EPMC4208311 | biostudies-literature

Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68.

Project description:Gamma-herpesviruses (gammaHVs) have developed an interaction with their hosts wherein they establish a life-long persistent infection and are associated with the onset of various malignancies. One critical virulence factor involved in the persistency of murine gamma-herpesvirus 68 (gammaHV68) is the viral homolog of the Bcl-2 protein (vBcl-2), which has been implicated to counteract both host apoptotic responses and autophagy pathway. However, the relative significance of the two activities of vBcl-2 in viral persistent infection has yet to be elucidated. Here, by characterizing a series of loss-of-function mutants of vBcl-2, we have distinguished the vBcl-2-mediated antagonism of autophagy from the vBcl-2-mediated inhibition of apoptosis in vitro and in vivo. A mutant gammaHV68 virus lacking the anti-autophagic activity of vBcl-2 demonstrates an impaired ability to maintain chronic infections in mice, whereas a mutant virus lacking the anti-apoptotic activity of vBcl-2 establishes chronic infections as efficiently as the wild-type virus but displays a compromised ability for ex vivo reactivation. Thus, the vBcl-2-mediated antagonism of host autophagy constitutes a novel mechanism by which gammaHVs confer persistent infections, further underscoring the importance of autophagy as a critical host determinant in the in vivo latency of gamma-herpesviruses.

| S-EPMC2752191 | biostudies-literature

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