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Proteomes, Volume 11, Issue 1 (March 2023) – 10 articles

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17 pages, 4165 KiB  
Article
Optimized Proteome Reduction for Integrative Top–Down Proteomics
by Breyer Woodland, Aleksandar Necakov and Jens R. Coorssen
Proteomes 2023, 11(1), 10; https://doi.org/10.3390/proteomes11010010 - 06 Mar 2023
Cited by 1 | Viewed by 2273
Abstract
Integrative top–down proteomics is an analytical approach that fully addresses the breadth and complexity needed for effective and routine assessment of proteomes. Nonetheless, any such assessments also require a rigorous review of methodology to ensure the deepest possible quantitative proteome analyses. Here, we [...] Read more.
Integrative top–down proteomics is an analytical approach that fully addresses the breadth and complexity needed for effective and routine assessment of proteomes. Nonetheless, any such assessments also require a rigorous review of methodology to ensure the deepest possible quantitative proteome analyses. Here, we establish an optimized general protocol for proteome extracts to improve the reduction of proteoforms and, thus, resolution in 2DE. Dithiothreitol (DTT), tributylphosphine (TBP), and 2-hydroxyethyldisulfide (HED), combined and alone, were tested in one-dimensional SDS-PAGE (1DE), prior to implementation into a full 2DE protocol. Prior to sample rehydration, reduction with 100 mM DTT + 5 mM TBP yielded increased spot counts, total signal, and spot circularity (i.e., decreased streaking) compared to other conditions and reduction protocols reported in the literature. The data indicate that many widely implemented reduction protocols are significantly ‘under-powered’ in terms of proteoform reduction and thus, limit the quality and depth of routine top–down proteomic analyses. Full article
(This article belongs to the Section Proteomics Technology and Methodology Development)
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18 pages, 3144 KiB  
Article
Analysis of the Interactome of the Toxoplasma gondii Tgj1 HSP40 Chaperone
by Jonathan Munera López, Andrés Mariano Alonso, Maria Julia Figueras, Ana María Saldarriaga Cartagena, Miryam A. Hortua Triana, Luis Diambra, Laura Vanagas, Bin Deng, Silvia N. J. Moreno and Sergio Oscar Angel
Proteomes 2023, 11(1), 9; https://doi.org/10.3390/proteomes11010009 - 01 Mar 2023
Cited by 2 | Viewed by 2189
Abstract
Toxoplasma gondii is an obligate intracellular apicomplexan that causes toxoplasmosis in humans and animals. Central to its dissemination and pathogenicity is the ability to rapidly divide in the tachyzoite stage and infect any type of nucleated cell. Adaptation to different cell contexts requires [...] Read more.
Toxoplasma gondii is an obligate intracellular apicomplexan that causes toxoplasmosis in humans and animals. Central to its dissemination and pathogenicity is the ability to rapidly divide in the tachyzoite stage and infect any type of nucleated cell. Adaptation to different cell contexts requires high plasticity in which heat shock proteins (Hsps) could play a fundamental role. Tgj1 is a type I Hsp40 of T. gondii, an ortholog of the DNAJA1 group, which is essential during the tachyzoite lytic cycle. Tgj1 consists of a J-domain, ZFD, and DNAJ_C domains with a CRQQ C-terminal motif, which is usually prone to lipidation. Tgj1 presented a mostly cytosolic subcellular localization overlapping partially with endoplasmic reticulum. Protein–protein Interaction (PPI) analysis showed that Tgj1 could be implicated in various biological pathways, mainly translation, protein folding, energy metabolism, membrane transport and protein translocation, invasion/pathogenesis, cell signaling, chromatin and transcription regulation, and cell redox homeostasis among others. The combination of Tgj1 and Hsp90 PPIs retrieved only 70 interactors linked to the Tgj1-Hsp90 axis, suggesting that Tgj1 would present specific functions in addition to those of the Hsp70/Hsp90 cycle, standing out invasion/pathogenesis, cell shape motility, and energy pathway. Within the Hsp70/Hsp90 cycle, translation-associated pathways, cell redox homeostasis, and protein folding were highly enriched in the Tgj1-Hsp90 axis. In conclusion, Tgj1 would interact with a wide range of proteins from different biological pathways, which could suggest a relevant role in them. Full article
(This article belongs to the Section Microbial Proteomics)
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20 pages, 1739 KiB  
Article
Non-Specific Signal Peptidase Processing of Extracellular Proteins in Staphylococcus aureus N315
by Santosh A. Misal, Shital D. Ovhal, Sujun Li, Jonathan A. Karty, Haixu Tang, Predrag Radivojac and James P. Reilly
Proteomes 2023, 11(1), 8; https://doi.org/10.3390/proteomes11010008 - 11 Feb 2023
Viewed by 1894
Abstract
Staphylococcus aureus is one of the major community-acquired human pathogens, with growing multidrug-resistance, leading to a major threat of more prevalent infections to humans. A variety of virulence factors and toxic proteins are secreted during infection via the general secretory (Sec) pathway, which [...] Read more.
Staphylococcus aureus is one of the major community-acquired human pathogens, with growing multidrug-resistance, leading to a major threat of more prevalent infections to humans. A variety of virulence factors and toxic proteins are secreted during infection via the general secretory (Sec) pathway, which requires an N-terminal signal peptide to be cleaved from the N-terminus of the protein. This N-terminal signal peptide is recognized and processed by a type I signal peptidase (SPase). SPase-mediated signal peptide processing is the crucial step in the pathogenicity of S. aureus. In the present study, the SPase-mediated N-terminal protein processing and their cleavage specificity were evaluated using a combination of N-terminal amidination bottom-up and top-down proteomics-based mass spectrometry approaches. Secretory proteins were found to be cleaved by SPase, specifically and non-specifically, on both sides of the normal SPase cleavage site. The non-specific cleavages occur at the relatively smaller residues that are present next to the −1, +1, and +2 locations from the original SPase cleavage site to a lesser extent. Additional random cleavages at the middle and near the C-terminus of some protein sequences were also observed. This additional processing could be a part of some stress conditions and unknown signal peptidase mechanisms. Full article
(This article belongs to the Section Microbial Proteomics)
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15 pages, 2335 KiB  
Article
Enzymatic Investigation of Spongospora subterranea Zoospore Attachment to Roots of Potato Cultivars Resistant or Susceptible to Powdery Scab Disease
by Xian Yu, Richard Wilson, Alieta Eyles, Sadegh Balotf, Robert Stephen Tegg and Calum Rae Wilson
Proteomes 2023, 11(1), 7; https://doi.org/10.3390/proteomes11010007 - 09 Feb 2023
Cited by 2 | Viewed by 1864
Abstract
For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. This study investigated [...] Read more.
For potato crops, host resistance is currently the most effective and sustainable tool to manage diseases caused by the plasmodiophorid Spongospora subterranea. Arguably, zoospore root attachment is the most critical phase of infection; however, the underlying mechanisms remain unknown. This study investigated the potential role of root-surface cell-wall polysaccharides and proteins in cultivars resistant/susceptible to zoospore attachment. We first compared the effects of enzymatic removal of root cell-wall proteins, N-linked glycans and polysaccharides on S. subterranea attachment. Subsequent analysis of peptides released by trypsin shaving (TS) of root segments identified 262 proteins that were differentially abundant between cultivars. These were enriched in root-surface-derived peptides but also included intracellular proteins, e.g., proteins associated with glutathione metabolism and lignin biosynthesis, which were more abundant in the resistant cultivar. Comparison with whole-root proteomic analysis of the same cultivars identified 226 proteins specific to the TS dataset, of which 188 were significantly different. Among these, the pathogen-defence-related cell-wall protein stem 28 kDa glycoprotein and two major latex proteins were significantly less abundant in the resistant cultivar. A further major latex protein was reduced in the resistant cultivar in both the TS and whole-root datasets. In contrast, three glutathione S-transferase proteins were more abundant in the resistant cultivar (TS-specific), while the protein glucan endo-1,3-beta-glucosidase was increased in both datasets. These results imply a particular role for major latex proteins and glucan endo-1,3-beta-glucosidase in regulating zoospore binding to potato roots and susceptibility to S. subterranea. Full article
(This article belongs to the Section Plant Proteomics)
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17 pages, 2672 KiB  
Article
Comprehensive Kinase Activity Profiling Revealed the Kinase Activity Patterns Associated with the Effects of EGFR Tyrosine Kinase Inhibitor Therapy in Advanced Non-Small-Cell Lung Cancer Patients with Sensitizing EGFR Mutations
by Rei Noguchi, Akihiro Yoshimura, Junji Uchino, Takayuki Takeda, Yusuke Chihara, Takayo Ota, Osamu Hiranuma, Hiroshi Gyotoku, Koichi Takayama and Tadashi Kondo
Proteomes 2023, 11(1), 6; https://doi.org/10.3390/proteomes11010006 - 05 Feb 2023
Cited by 1 | Viewed by 2052
Abstract
EGFR mutations are strong predictive markers for EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients with non-small-cell lung cancer (NSCLC). Although NSCLC patients with sensitizing EGFR mutations have better prognoses, some patients exhibit worse prognoses. We hypothesized that various activities of kinases could [...] Read more.
EGFR mutations are strong predictive markers for EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy in patients with non-small-cell lung cancer (NSCLC). Although NSCLC patients with sensitizing EGFR mutations have better prognoses, some patients exhibit worse prognoses. We hypothesized that various activities of kinases could be potential predictive biomarkers for EGFR-TKI treatment among NSCLC patients with sensitizing EGFR mutations. In 18 patients with stage IV NSCLC, EGFR mutations were detected and comprehensive kinase activity profiling was performed using the peptide array PamStation12 for 100 tyrosine kinases. Prognoses were observed prospectively after the administration of EGFR-TKIs. Finally, the kinase profiles were analyzed in combination with the prognoses of the patients. Comprehensive kinase activity analysis identified specific kinase features, consisting of 102 peptides and 35 kinases, in NSCLC patients with sensitizing EGFR mutations. Network analysis revealed seven highly phosphorylated kinases: CTNNB1, CRK, EGFR, ERBB2, PIK3R1, PLCG1, and PTPN11. Pathway analysis and Reactome analysis revealed that the PI3K-AKT and RAF/ MAPK pathways were significantly enriched in the poor prognosis group, being consistent with the outcome of the network analysis. Patients with poor prognoses exhibited high activation of EGFR, PIK3R1, and ERBB2. Comprehensive kinase activity profiles may provide predictive biomarker candidates for screening patients with advanced NSCLC harboring sensitizing EGFR mutations. Full article
(This article belongs to the Section Proteomics of Human Diseases and Their Treatments)
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14 pages, 1032 KiB  
Review
The Double-Edged Proteins in Cancer Proteomes and the Generation of Induced Tumor-Suppressing Cells (iTSCs)
by Kexin Li, Qingji Huo, Bai-Yan Li and Hiroki Yokota
Proteomes 2023, 11(1), 5; https://doi.org/10.3390/proteomes11010005 - 18 Jan 2023
Cited by 3 | Viewed by 2036
Abstract
Unlike a prevalent expectation that tumor cells secrete tumor-promoting proteins and stimulate the progression of neighboring tumor cells, accumulating evidence indicates that the role of tumor-secreted proteins is double-edged and context-dependent. Some of the oncogenic proteins in the cytoplasm and cell membranes, which [...] Read more.
Unlike a prevalent expectation that tumor cells secrete tumor-promoting proteins and stimulate the progression of neighboring tumor cells, accumulating evidence indicates that the role of tumor-secreted proteins is double-edged and context-dependent. Some of the oncogenic proteins in the cytoplasm and cell membranes, which are considered to promote the proliferation and migration of tumor cells, may inversely act as tumor-suppressing proteins in the extracellular domain. Furthermore, the action of tumor-secreted proteins by aggressive “super-fit” tumor cells can be different from those derived from “less-fit” tumor cells. Tumor cells that are exposed to chemotherapeutic agents could alter their secretory proteomes. Super-fit tumor cells tend to secrete tumor-suppressing proteins, while less-fit or chemotherapeutic agent-treated tumor cells may secrete tumor-promotive proteomes. Interestingly, proteomes derived from nontumor cells such as mesenchymal stem cells and peripheral blood mononuclear cells mostly share common features with tumor cell-derived proteomes in response to certain signals. This review introduces the double-sided functions of tumor-secreted proteins and describes the proposed underlying mechanism, which would possibly be based on cell competition. Full article
(This article belongs to the Special Issue Proteomics in Cancer Research)
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2 pages, 198 KiB  
Editorial
Acknowledgment to the Reviewers of Proteomes in 2022
by Proteomes Editorial Office
Proteomes 2023, 11(1), 4; https://doi.org/10.3390/proteomes11010004 - 13 Jan 2023
Viewed by 928
Abstract
High-quality academic publishing is built on rigorous peer review [...] Full article
20 pages, 4068 KiB  
Article
Characterisation of Colorectal Cancer Cell Lines through Proteomic Profiling of Their Extracellular Vesicles
by Kathleen A. Heck, Håvard T. Lindholm, Barbara Niederdorfer, Eirini Tsirvouli, Martin Kuiper, Åsmund Flobak, Astrid Lægreid and Liv Thommesen
Proteomes 2023, 11(1), 3; https://doi.org/10.3390/proteomes11010003 - 11 Jan 2023
Cited by 2 | Viewed by 2749
Abstract
Colorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which are present in liquid biopsies. Here, we characterised the proteome landscape [...] Read more.
Colorectal cancer (CRC) is one of the most prevalent cancers, driven by several factors including deregulations in intracellular signalling pathways. Small extracellular vesicles (sEVs) are nanosized protein-packaged particles released from cells, which are present in liquid biopsies. Here, we characterised the proteome landscape of sEVs and their cells of origin in three CRC cell lines HCT116, HT29 and SW620 to explore molecular traits that could be exploited as cancer biomarker candidates and how intracellular signalling can be assessed by sEV analysis instead of directly obtaining the cell of origin itself. Our findings revealed that sEV cargo clearly reflects its cell of origin with proteins of the PI3K-AKT pathway highly represented in sEVs. Proteins known to be involved in CRC were detected in both cells and sEVs including KRAS, ARAF, mTOR, PDPK1 and MAPK1, while TGFB1 and TGFBR2, known to be key players in epithelial cancer carcinogenesis, were found to be enriched in sEVs. Furthermore, the phosphopeptide-enriched profiling of cell lysates demonstrated a distinct pattern between cell lines and highlighted potential phosphoproteomic targets to be investigated in sEVs. The total proteomic and phosphoproteomics profiles described in the current work can serve as a source to identify candidates for cancer biomarkers that can potentially be assessed from liquid biopsies. Full article
(This article belongs to the Section Extracellular Vesicles)
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66 pages, 1761 KiB  
Review
Advancements in Oncoproteomics Technologies: Treading toward Translation into Clinical Practice
by Ankita Punetha and Deepak Kotiya
Proteomes 2023, 11(1), 2; https://doi.org/10.3390/proteomes11010002 - 10 Jan 2023
Cited by 3 | Viewed by 4712
Abstract
Proteomics continues to forge significant strides in the discovery of essential biological processes, uncovering valuable information on the identity, global protein abundance, protein modifications, proteoform levels, and signal transduction pathways. Cancer is a complicated and heterogeneous disease, and the onset and progression involve [...] Read more.
Proteomics continues to forge significant strides in the discovery of essential biological processes, uncovering valuable information on the identity, global protein abundance, protein modifications, proteoform levels, and signal transduction pathways. Cancer is a complicated and heterogeneous disease, and the onset and progression involve multiple dysregulated proteoforms and their downstream signaling pathways. These are modulated by various factors such as molecular, genetic, tissue, cellular, ethnic/racial, socioeconomic status, environmental, and demographic differences that vary with time. The knowledge of cancer has improved the treatment and clinical management; however, the survival rates have not increased significantly, and cancer remains a major cause of mortality. Oncoproteomics studies help to develop and validate proteomics technologies for routine application in clinical laboratories for (1) diagnostic and prognostic categorization of cancer, (2) real-time monitoring of treatment, (3) assessing drug efficacy and toxicity, (4) therapeutic modulations based on the changes with prognosis and drug resistance, and (5) personalized medication. Investigation of tumor-specific proteomic profiles in conjunction with healthy controls provides crucial information in mechanistic studies on tumorigenesis, metastasis, and drug resistance. This review provides an overview of proteomics technologies that assist the discovery of novel drug targets, biomarkers for early detection, surveillance, prognosis, drug monitoring, and tailoring therapy to the cancer patient. The information gained from such technologies has drastically improved cancer research. We further provide exemplars from recent oncoproteomics applications in the discovery of biomarkers in various cancers, drug discovery, and clinical treatment. Overall, the future of oncoproteomics holds enormous potential for translating technologies from the bench to the bedside. Full article
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18 pages, 781 KiB  
Review
The Need for Biomarkers in the ALS–FTD Spectrum: A Clinical Point of View on the Role of Proteomics
by Francesca Vignaroli, Angelica Mele, Giacomo Tondo, Veronica De Giorgis, Marcello Manfredi, Cristoforo Comi, Letizia Mazzini and Fabiola De Marchi
Proteomes 2023, 11(1), 1; https://doi.org/10.3390/proteomes11010001 - 09 Jan 2023
Cited by 6 | Viewed by 2683
Abstract
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are severely debilitating and progressive neurodegenerative disorders. A distinctive pathological feature of several neurodegenerative diseases, including ALS and FTD, is the deposition of aberrant protein inclusions in neuronal cells, which leads to cellular dysfunction and [...] Read more.
Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are severely debilitating and progressive neurodegenerative disorders. A distinctive pathological feature of several neurodegenerative diseases, including ALS and FTD, is the deposition of aberrant protein inclusions in neuronal cells, which leads to cellular dysfunction and neuronal damage and loss. Despite this, to date, the biological process behind developing these protein inclusions must be better clarified, making the development of disease-modifying treatment impossible until this is done. Proteomics is a powerful tool to characterize the expression, structure, functions, interactions, and modifications of proteins of tissue and biological fluid, including plasma, serum, and cerebrospinal fluid. This protein-profiling characterization aims to identify disease-specific protein alteration or specific pathology-based mechanisms which may be used as markers of these conditions. Our narrative review aims to highlight the need for biomarkers and the potential use of proteomics in clinical practice for ALS–FTD spectrum disorders, considering the emerging rationale in proteomics for new drug development. Certainly, new data will emerge in the near future in this regard and support clinicians in the development of personalized medicine. Full article
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