Combined treatment of human multiple myeloma cells with bortezomib and doxorubicin alters the interactome of 20S proteasomes

Mittenberg, A. G.; Kuzyk, Valeria O.; Shabelnikov, Sergey; Gorbach, Daria P.; Shatrova, A. N.; Fedorova, Olga; Barlev, Nikolai A.

doi:10.1080/15384101.2018.1496742

Cited by 10 publications

(8 citation statements)

References 54 publications

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“…The P20S β5 subunit is the known chymotrypsin-like catalytic subunit for SUC-LLVY-AMC [48]. The P20S α3 subunit is a cornerstone structural subunit that interacts with many different proteins and functions as a putative core particle gatekeeper [49]. The P20S α3 subunit also has a role in RNA metabolism, cell death, and cell cycle control [50,51], which could be important to oligodendrocytes in immature white matter after HI [23,34].…”

Section: Western Blot Analysismentioning

confidence: 99%

Oleuropein Activates Neonatal Neocortical Proteasomes, but Proteasome Gene Targeting by AAV9 Is Variable in a Clinically Relevant Piglet Model of Brain Hypoxia-Ischemia and Hypothermia

Demerdash

Chen

O’Brien

et al. 2021

Cells

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Cerebral hypoxia-ischemia (HI) compromises the proteasome in a clinically relevant neonatal piglet model. Protecting and activating proteasomes could be an adjunct therapy to hypothermia. We investigated whether chymotrypsin-like proteasome activity differs regionally and developmentally in the neonatal brain. We also tested whether neonatal brain proteasomes can be modulated by oleuropein, an experimental pleiotropic neuroprotective drug, or by targeting a proteasome subunit gene using recombinant adeno-associated virus-9 (AAV). During post-HI hypothermia, we treated piglets with oleuropein, used AAV-short hairpin RNA (shRNA) to knock down proteasome activator 28γ (PA28γ), or enforced PA28γ using AAV-PA28γ with green fluorescent protein (GFP). Neonatal neocortex and subcortical white matter had greater proteasome activity than did liver and kidney. Neonatal white matter had higher proteasome activity than did juvenile white matter. Lower arterial pH 1 h after HI correlated with greater subsequent cortical proteasome activity. With increasing brain homogenate protein input into the assay, the initial proteasome activity increased only among shams, whereas HI increased total kinetic proteasome activity. OLE increased the initial neocortical proteasome activity after hypothermia. AAV drove GFP expression, and white matter PA28γ levels correlated with proteasome activity and subunit levels. However, AAV proteasome modulation varied. Thus, neonatal neocortical proteasomes can be pharmacologically activated. HI slows the initial proteasome performance, but then augments ongoing catalytic activity. AAV-mediated genetic manipulation in the piglet brain holds promise, though proteasome gene targeting requires further development.

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Section: Western Blot Analysismentioning

confidence: 99%

Oleuropein Activates Neonatal Neocortical Proteasomes, but Proteasome Gene Targeting by AAV9 Is Variable in a Clinically Relevant Piglet Model of Brain Hypoxia-Ischemia and Hypothermia

Demerdash

Chen

O’Brien

et al. 2021

Cells

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“…For MALDI TOF/TOF (tandem time-of-flight mass spectrometry (MS/MS) mass spectrometry, the trypsin digested (Trypsin Gold, Madison, WI, USA) protein samples were analyzed with an AB Sciex TOF/TOF 5800 System (SCIEX, Darmstadt, Germany) instrument operated in the positive ion mode [ 24 ]. The MALDI stage was set to continuous motion mode.…”

Section: Methodsmentioning

confidence: 99%

Proteomics Answers Which Yeast Genes Are Specific for Baking, Brewing, and Ethanol Production

Davydenko¹,

Meledina

Mittenberg

et al. 2020

Bioengineering

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Yeast strains are convenient models for studying domestication processes. The ability of yeast to ferment carbon sources from various substrates and to produce ethanol and carbon dioxide is the core of brewing, winemaking, and ethanol production technologies. The present study reveals the differences among yeast strains used in various industries. To understand this, we performed a proteomic study of industrial Saccharomyces cerevisiae strains followed by a comparative analysis of available yeast genetic data. Individual protein expression levels in domesticated strains from different industries indicated modulation resulting from response to technological environments. The innovative nature of this research was the discovery of genes overexpressed in yeast strains adapted to brewing, baking, and ethanol production, typical genes for specific domestication were found. We discovered a gene set typical for brewer’s yeast strains. Baker’s yeast had a specific gene adapted to osmotic stress. Toxic stress was typical for yeast used for ethanol production. The data obtained can be applied for targeted improvement of industrial strains.

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“…It was recently reported that the C-terminal region of the proteasome α7 subunit (or PSMA3) could play the role of substrate receptor for IDPs. 22,34 Thus, we hypothesized that even blocked by epoxomicin, the 20S proteasome could immobilize part of the galectin-3 pool, through interaction of the lectin N-terminal disordered region with the C-terminal region of proteasome α7 subunit, and therefore could impair hemagglutination (Figure 8B). To test this hypothesis, 20S proteasome was blocked by epoxomicin and incubated with biotinylated galectin-3 before loading onto a sucrose gradient.…”

Section: Functional Features Of Secreted Proteasome Collected From Ce...mentioning

confidence: 99%

Extracellular 20S proteasome secreted via microvesicles can degrade poorly folded proteins and inhibit Galectin‐3 agglutination activity

Bonhoure¹,

Henry

Bich

et al. 2022

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Proteasomes are major non‐lysosomal proteolytic complexes localized in the cytoplasm and in the nucleus of eukaryotic cells. Strikingly, high levels of extracellular proteasome have also been evidenced in the plasma (p‐proteasome) of patients with specific diseases. Here, we examined the process by which proteasomes are secreted, as well as their structural and functional features once in the extracellular space. We demonstrate that assembled 20S core particles are secreted by cells within microvesicles budding from the plasma membrane. Part of the extracellular proteasome pool is also free of membranes in the supernatant of cultured cells, and likely originates from microvesicles leakage. We further demonstrate that this free proteasome released by cells (cc‐proteasome for cell culture proteasome) possesses latent proteolytic activity and can degrade various extracellular proteins. Both standard (no immune‐subunits) and intermediate (containing some immune‐subunits) forms of 20S are observed. Moreover, we show that galectin‐3, which displays a highly disordered N‐terminal region, is efficiently cleaved by purified cc‐proteasome, without SDS activation, likely after its binding to PSMA3 (α7) subunit through its intrinsically disordered region. As a consequence, galectin‐3 is unable to induce red blood cells agglutination when preincubated with cc‐proteasome. These results highlight potential novel physio‐ and pathologic functions for the extracellular proteasome.

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Combined treatment of human multiple myeloma cells with bortezomib and doxorubicin alters the interactome of 20S proteasomes

Cited by 10 publications

References 54 publications

Oleuropein Activates Neonatal Neocortical Proteasomes, but Proteasome Gene Targeting by AAV9 Is Variable in a Clinically Relevant Piglet Model of Brain Hypoxia-Ischemia and Hypothermia

Oleuropein Activates Neonatal Neocortical Proteasomes, but Proteasome Gene Targeting by AAV9 Is Variable in a Clinically Relevant Piglet Model of Brain Hypoxia-Ischemia and Hypothermia

Proteomics Answers Which Yeast Genes Are Specific for Baking, Brewing, and Ethanol Production

Extracellular 20S proteasome secreted via microvesicles can degrade poorly folded proteins and inhibit Galectin‐3 agglutination activity

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