Emerging role of immunoproteasomes in pathophysiology

Kaur, Gagandeep; Batra, Sanjay

doi:10.1038/icb.2016.50

Cited by 40 publications

(26 citation statements)

References 68 publications

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“…Since the primary role of the immunoproteasome is to process antigens for presentation on major histocompatibility complex (MHC) class I molecules to CD8 + T lymphocytes, the immunoproteasome degrades various proteins, including viral proteins [ 30 ]. Therefore, the immunoproteasome plays an important role during viral and bacterial infections [ 31 ]. The expression of the immunoproteasome is induced by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) under inflammatory conditions, such as infections and autoimmune diseases in the presence of inflammatory cytokines [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Serum Extracellular Vesicles (EVs) from Atlantic Salmon Infected with Piscirickettsia Salmonis

et al. 2017

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Secretion of extracellular vesicles (EVs) is a common feature of both eukaryotic and prokaryotic cells. Isolated EVs have been shown to contain different types of molecules, including proteins and nucleic acids, and are reported to be key players in intercellular communication. Little is known, however, of EV secretion in fish, or the effect of infection on EV release and content. In the present study, EVs were isolated from the serum of healthy and Piscirickettsia salmonis infected Atlantic salmon in order to evaluate the effect of infection on EV secretion. P. salmonis is facultative intracellular bacterium that causes a systemic infection disease in farmed salmonids. EVs isolated from both infected and non-infected fish had an average diameter of 230–300 nm, as confirmed by transmission electron microscopy, nanoparticle tracking, and flow cytometry. Mass spectrometry identified 180 proteins in serum EVs from both groups of fish. Interestingly, 35 unique proteins were identified in serum EVs isolated from the fish infected with P. salmonis. These unique proteins included proteasomes subunits, granulins, and major histocompatibility class I and II. Our results suggest that EV release could be part of a mechanism in which host stimulatory molecules are released from infected cells to promote an immune response.

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Serum Extracellular Vesicles (EVs) from Atlantic Salmon Infected with Piscirickettsia Salmonis

et al. 2017

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“…The lack of selectivity of bortezomib and carfilzomib against cCP and iCP leads to the undesired inhibition of cCP in normal cells and in part explain the side effects and resistance observed during treatments of multiple myeloma with these drugs [23,24]. Selective inhibitors of immunoproteasome are thought to lead to clinical benefits in the treatment of several diseases such as neurodegenerative diseases, inflammation, autoimmune disorders and certain types of cancer [25]. These expected benefits explain the current focus on selective immunoproteasome inhibitors.…”

Section: Resultsmentioning

confidence: 99%

Piperlongumine and some of its analogs inhibit selectively the human immunoproteasome over the constitutive proteasome

Bosc

Nastri

Lefort

et al. 2018

Biochemical and Biophysical Research Communications

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The natural small molecule piperlongumine A is toxic selectively to cancer cells in vitro and in vivo. This toxicity has been correlated with cancer cell ROS, DNA damage and apoptotic cell death increases. We demonstrate here a new mechanistic property of piperlongumine: it inhibits selectively human immunoproteasome with no noticeable inhibition of human constitutive proteasome. This result suggests that immunoproteasome inhibition, a mechanism independent of ROS elevation, may also partly play a role in the anticancer effects observed with piperlongumine. Structure-activity relationships of piperlongumine analogs suggest that the lactam (piperidonic) ring of piperlongumine A may be replaced by the linear olefin -NHCO-CH=CH to improve both in vitro inhibitory efficiency against immunoproteasome and cellular toxicity.

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“…The selective i-20S inhibitor carfilzomib has shown clinical activity in vitro in primary CD34 + PMF cells and it is safe in combination with ruxolitinib in patients affected by several hematological malignancies (clinical trial.gov, NCT03773107), suggesting that targeting IPs is worth being investigated in PMF. We must bear in mind that, abnormal MHC class I expression and the loss of antigen processing are features of malignant cells [71]. T cell-mediated immune tumor suppression is a complex process with numerous requirements, among which is antigen processing by the IPs and presentation through MHC class I surface molecules expressed on tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Immunoproteasome Genes Are Modulated in CD34+ JAK2V617F Mutated Cells from Primary Myelofibrosis Patients

Rosa

Giallongo

Romano

et al. 2020

IJMS

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Primary myelofibrosis (PMF) is a rare myeloproliferative neoplasm characterized by stem-cell-derived clonal over-proliferation of mature myeloid lineages, bone marrow fibrosis, osteosclerosis, defective erythropoiesis, and pro-inflammatory cytokine over-expression. The aim of the present study was to highlight possible differences in the transcriptome among CD34+ cells from peripheral blood (PB) of PMF patients. Therefore, we merged two microarray datasets of healthy control subjects and PMF (34 JAK2V617F MUTATED and 28 JAK2 wild-type). The GO analysis of upregulated genes revealed enrichment for JAK2/STAT1 pathway gene set in PB CD34+ cells of PMF patients with and without the JAK2V617F mutation comparing to the healthy control subjects, and in particular a significant upregulation of immunoproteasome (IP)-belonging genes as PSMB8, PSMB9, and PSMB10. A more detailed investigation of the IFN-gamma (IFNG) pathway also revealed that IFNG, IRF1, and IFNGR2 were significantly upregulated in PB CD34+ cells of PMF patients carrying the mutation for JAK2V617F compared to JAK2 wild-type PMF patients. Finally, we showed an upregulation of HLA-class I genes in PB CD34+ cells from PMF JAK2V617F mutated patients compared to JAK2 wild-type and healthy controls. In conclusion, our results demonstrate that IPs and IFNG pathways could be involved in PMF disease and in particular in patients carrying the JAK2V617F mutation.

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Emerging role of immunoproteasomes in pathophysiology

Cited by 40 publications

References 68 publications

Isolation and Characterization of Serum Extracellular Vesicles (EVs) from Atlantic Salmon Infected with Piscirickettsia Salmonis

Isolation and Characterization of Serum Extracellular Vesicles (EVs) from Atlantic Salmon Infected with Piscirickettsia Salmonis

Piperlongumine and some of its analogs inhibit selectively the human immunoproteasome over the constitutive proteasome

Immunoproteasome Genes Are Modulated in CD34+ JAK2V617F Mutated Cells from Primary Myelofibrosis Patients

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