ER stress affects processing of MHC class I-associated peptides

Granados, Diana Paola; Tanguay, Pierre‐Luc; Hardy, Marie-Pierre; Caron, Étienne; Verteuil, Danielle de; Meloche, Sylvain; Perreault, Claude

doi:10.1186/1471-2172-10-10

Cited by 110 publications

(92 citation statements)

References 73 publications

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“…Exposure to ER stress conditions cells for survival, decreases levels of HLA class I proteins at the cell surface and decreases the synthesis of new HLA class I molecules. This prepares cells for subsequent, more severe stress (40,48). We show evidence of the regulation of ERp57 at the cellular level by the amounts of glucose in the medium.…”

Section: Discussionmentioning

confidence: 63%

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A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis

Santana-Codina

Carretero

Sanz‐Pamplona

et al. 2013

Molecular & Cellular Proteomics

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Bone metastasis is the most common distant relapse in breast cancer. The identification of key proteins involved in the osteotropic phenotype would represent a major step toward the development of new prognostic markers and therapeutic improvements. The aim of this study was to characterize functional phenotypes that favor bone metastasis in human breast cancer. We used the human breast cancer cell line MDA-MB-231 and its osteotropic BO2 subclone to identify crucial proteins in bone metastatic growth. We identified 31 proteins, 15 underexpressed and 16 overexpressed, in BO2 cells compared with parental cells. We employed a network-modeling approach in which these 31 candidate proteins were prioritized with respect to their potential in metastasis formation, based on the topology of the protein-protein interaction network and differential expression. The protein-protein interaction network provided a framework to study the functional relationships between biological molecules by attributing functions to genes whose functions had not been characterized. The combination of expression profiles and protein interactions revealed an endoplasmic reticulum-thiol oxidoreductase, ERp57, function- Large-scale genomic analysis has provided a wealth of information on biologically relevant systems, and the ability to analyze this information is crucial to uncovering important biological relationships. In breast cancer, microarray gene expression analysis is a promising technique for providing consistent patterns of variation in bone metastasis gene expression; the most common metastasis (80%) in those women who progress to an advanced stage of disease (1-4). However, a large number of genes with many diverse functions are identified as prognostic markers, without revealing much about the underlying biological mechanism.Genes that enhance or suppress bone metastasis are associated with multiple cellular processes that normally occur during metastasis progression, including survival and proliferation in the bone marrow microenvironment, and modification of bone structure and function (1). Many genes in this group encode secretory or cell surface proteins involved in cell homing to bone, angiogenesis, invasion, and osteoclast recruitment (1, 2, 5). Moreover, emerging evidence from murine models suggests that tumor-specific endocrine factors systematically stimulate the quiescent bone marrow compartment (BM), resulting in a BM-derived tumor microenvironment From the ‡Biological Clues

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Section: Discussionmentioning

confidence: 63%

“…The role of ERp57 in the folding and assembly of HLA class I molecules has been reported (39,40). Therefore, we studied which HLA class I molecules and/or subunits of the antigenprocessing machinery (APM) could be affected by ERp57 expression and whether the processing machinery might be involved.…”

Section: Identification Of Bone Metastatic Candidatementioning

confidence: 99%

A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis

Santana-Codina

Carretero

Sanz‐Pamplona

et al. 2013

Molecular & Cellular Proteomics

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“…We showed that, although B cells mounting an UPR following accumulation of a KDEL-retained protein in the ER upregulate MHC class II and costimulatory molecules (72), they present decreased levels of high-affinity peptide complexed to MHC class II. Similarly, mouse thymoma cells under palmitate or glucose deprivation-induced ER stress decrease transgenic OVA Ag presentation on MHC class I (73). These findings begin to suggest that APC under ER stress undergo remodeling of the processing machinery, yielding decreased presentation of high-affinity immunodominant peptides and increased presentation of subdominant or low-affinity peptides.…”

Section: The Upr Intersects With Cellular Proinflammationmentioning

confidence: 87%

Tumor Stress Inside Out: Cell-Extrinsic Effects of the Unfolded Protein Response in Tumor Cells Modulate the Immunological Landscape of the Tumor Microenvironment

Mahadevan

Zanetti

2011

The Journal of Immunology

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The unfolded protein response (UPR) is a eukaryotic cellular adaptive mechanism that functions to cope with stress of the endoplasmic reticulum (ER). Accumulating evidence demonstrates that the tumor microenvironment contains stressors that elicit a UPR, which has been demonstrated to be a cell-intrinsic mechanism crucial for tumorigenesis. In addition, the UPR is a source of proinflammatory signaling whose downstream mediators may hamper antitumor immunity. We discuss how the UPR may impair Ag presentation, which could result in defective T cell priming, also leading to tumor escape and growth. Further, we discuss the recent finding that ER stress and attendant proinflammation can be transmitted from ER-stressed tumor cells to myeloid cells. The ideas presented suggest that, in addition to being a cell-intrinsic mechanism of tumor survival, the tumor UPR can serve as a cell-extrinsic regulator of tumorigenesis by remodeling the immune response in the tumor microenvironment.

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“…Evidence also suggests that the UPR may blunt the antitumor immune response by affecting antigen presentation and antigen-presenting cells per se. Perturbation of the secretory pathway or ER stress decreases the presentation of high-affinity peptides by major histocompatibility complex (MHC) classes I and II (120,121). Moreover, UPR-dependent products that transfer from cancer cells to DCs trigger arginase activation (an enzyme that suppresses T cell function) (122) and hinder the ability of DCs to cross-present antigen and cross-prime CD8 + T cells (119).…”

Section: Er Proteostasis Control In Glioma Stromal Cells Gliomas Reprmentioning

confidence: 99%

Endoplasmic reticulum proteostasis in glioblastoma—From molecular mechanisms to therapeutic perspectives

et al. 2017

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ER stress affects processing of MHC class I-associated peptides

Cited by 110 publications

References 73 publications

A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis

A Transcriptome-proteome Integrated Network Identifies Endoplasmic Reticulum thiol oxidoreductase (ERp57) as a Hub that Mediates Bone Metastasis

Tumor Stress Inside Out: Cell-Extrinsic Effects of the Unfolded Protein Response in Tumor Cells Modulate the Immunological Landscape of the Tumor Microenvironment

Endoplasmic reticulum proteostasis in glioblastoma—From molecular mechanisms to therapeutic perspectives

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