Proteomics Data in Support of
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive
ORGANISM(S): Trichomonas Vaginalis (ncbitaxon:5722)
SUBMITTER: 
Anthony O'Donoghue
PROVIDER: MSV000083474 | MassIVE | Thu Feb 21 14:40:00 GMT 2019
REPOSITORIES: MassIVE
Similar Datasets
Project description:Proteomics data from gel band excision in support of "The proteasome as a drug target in the metazoan pathogen, Schistosoma mansoni"
2018-10-10 | MSV000083021 | MassIVE
Project description:We compared the expression changes in Ewing sarcoma cell lines following treatment with 2 known 20S proteasome inhibitors versus 2 novel compounds
2017-04-25 | GSE80640 | GEO
Project description:Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, especially in the points of rapid growth rate and microenvironment independency. Consequently, the majority of conventional anti-cancer drugs are less sensitive to slow growing cells and do not target microenvironmental support, although most primary cancer cells grow slower than cell lines and depend on microenvironmental support. Here, we developed a novel high throughput drug screening system using patient-derived xenograft (PDX) cells of lymphoma that maintained primary cancer cell phenotype more than cell lines. The library containing 2613 known pharmacologically active substance and off-patent drugs were screened by this system. We could find many compounds showing higher cytotoxicity than conventional anti-tumor drugs. Especially, pyruvinium pamoate showed the highest activity, and its strong anti-tumor effect was confirmed also in vivo. We extensively investigated its mechanism of action and found that it inhibited glutathione supply from stromal cells to lymphoma cells, implying the importance of the stromal protection from ox 1 idative stress for lymphoma cell survival and a new therapeutic strategy for lymphoma. Our system introduces a primary cancer cell phenotype into cell-based phenotype screening and sheds new light on anti-cancer drug development. Global gene expression profiles of PDX cells showed high similarity to those of original primary cells. The correlation coefficient of gene expression profiles between PDX cells and the originalprimary cells was 0.814-0.890.
2015-08-31 | E-GEOD-71944 | biostudies-arrayexpress
Project description:The 20S proteasome is responsible for the catalytic activity of all proteasome complexes. Structural constraints mean that only unfolded, extended polypeptide chains may enter the catalytic core of the 20S proteasome. Here we conducted a comprehensive analysis of the 20S CP substrates in-vitro. We revealed that the 20S CP substrates are highly structually disordered. The 20S proteasome substrate group, termed 20S-IDPome are characterized by having significantly more protein binding partners, more post-translational modification sites and are highly enriched for RNA binding proteins. Remarkably, we found that low complexity proteins with prion-like domain which interact with GR or PR di-peptide repeats are the most preferential 20S proteasome substrates. Our finding suggests roles of the 20S proteasome in gene transcription and formation of phase-separated granules.
2018-07-30 | PXD010132 | Pride
Project description:Mature Red Blood Cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. While growing inside RBCs, Pf are known to secrete multipurpose extracellular vesicles (EVs), yet their influence on this parasite’s essential host cell, the RBC, remains unknown. Here we demonstrate that Pf parasites export within such EVs assembled and functional 20S proteasome complexes (EV-20S). The EV-20S proteasomes modulate the mechanical properties of naïve host RBCs by remodeling the cytoskeleton network. Furthermore, we identified four novel degradation targets of the exported 20S proteasome, the phosphorylated cytoskelatal proteins β-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S proteasome export mechanism of Pf-iRBCs, which prime naïve RBC by altering membrane stiffness, to facilitate malaria parasite growth.
2021-01-04 | PXD018154 | Pride
Project description:We used Affymetrix Chicken Genome Array to identify transcripts differentially expressed between cells treated with DMIOA and control cells and between DMIOA and DMIOA+20S treated cells Preadipocytes isolated from laying hen were treated with DMIOA and DMIOA+20S to identify transcripts differentailly expressed between control cells and DMIOA treated and between DMIOA and DMIOA+20S treated cells
2013-09-17 | E-GEOD-50880 | biostudies-arrayexpress
Project description:Mature Red Blood Cells (RBCs) lack internal organelles and canonical defense mechanisms, making them both a fascinating host cell, in general, and an intriguing choice for the deadly malaria parasite Plasmodium falciparum (Pf), in particular. Pf, while growing inside its natural host, the human RBC, secretes multipurpose extracellular vesicles (EVs), yet their influence on this essential host cell remains unknown. Here we demonstrate that Pf parasites, cultured in fresh human donor blood, export within such EVs assembled and functional 20S proteasome complexes (EV-20S). The EV-20S proteasomes modulate the mechanical properties of naïve human RBCs by remodeling their cytoskeletal network. Furthermore, we identify four novel degradation targets of the exported 20S proteasome, the phosphorylated cytoskeletal proteins β-adducin, ankyrin-1, dematin and Epb4.1. Overall, our findings reveal a previously unknown 20S proteasome export mechanism employed by the human malaria parasite, which primes RBCs for parasite invasion by altering membrane stiffness, to facilitate malaria parasite growth.
2021-02-04 | PXD023353 | Pride
Project description:For many years, the ubiquitin-26S proteasome degradation pathway was considered the principal route for proteasomal degradation. However, it is now becoming clear that proteins can also be targeted for degradation by an ubiquitin-independent mechanism mediated by the core 20S proteasome itself. The fact that half of cellular proteasomes are free 20S complexes suggests that degradation by this complex is not limited to rare cases. Identifying 20S proteasome substrates is challenging, as different pools of the same protein can be sent to degradation via either 20S or 26S proteasomes. Hence, current knowledge regarding the repertoire of 20S proteasome substrates mainly originates from individual case studies. Here, in an effort to unravel the global repertoire of substrates degraded by the 20S proteasome, we used an advanced mass spectrometry approach coupled with biochemical and cellular analysis. Our analysis enabled the identification of hundreds of 20S proteasome substrates. In addition to proteins that are degraded to completion, we also identified proteins that undergo specific cleavage by the 20S proteasome, at their N- or C- termini, to possibly tune their function. We also found that 20S substrates are significantly enriched with RNA- and DNA-binding proteins that contain intrinsically disordered regions. The vast majority of them are localized in the nucleus and stress granules. Further, we demonstrate that oxidized proteasomes have reduced proteolytic activity compared to naïve proteasomes, which we propose is an adaptive advantage under conditions of cellular stress. Whereas oxidized protein substrates, rather than being folded proteins that lost their native structure due to the stress, actually display a higher degree of structural-disorder than naïve proteins. In summary, here we shed light on the nature of the 20S substrates, providing critical insight into the biological role of the 20S proteasome.
2023-12-21 | PXD044399 | Pride
Project description:Cell lines have been used for drug discovery as useful models of cancers; however, they do not recapitulate cancers faithfully, especially in the points of rapid growth rate and microenvironment independency. Consequently, the majority of conventional anti-cancer drugs are less sensitive to slow growing cells and do not target microenvironmental support, although most primary cancer cells grow slower than cell lines and depend on microenvironmental support. Here, we developed a novel high throughput drug screening system using patient-derived xenograft (PDX) cells of lymphoma that maintained primary cancer cell phenotype more than cell lines. The library containing 2613 known pharmacologically active substance and off-patent drugs were screened by this system. We could find many compounds showing higher cytotoxicity than conventional anti-tumor drugs. Especially, pyruvinium pamoate showed the highest activity, and its strong anti-tumor effect was confirmed also in vivo. We extensively investigated its mechanism of action and found that it inhibited glutathione supply from stromal cells to lymphoma cells, implying the importance of the stromal protection from ox 1 idative stress for lymphoma cell survival and a new therapeutic strategy for lymphoma. Our system introduces a primary cancer cell phenotype into cell-based phenotype screening and sheds new light on anti-cancer drug development.
2015-08-31 | GSE71944 | GEO