Journal of proteomics最新文献

{"title":"Combining information on degradomics and gene expression data in prospecting metastatic melanoma proteolytic signatures","authors":"Murilo Salardani ,&nbsp;Alison F.A. Chaves ,&nbsp;Leonardo Cardili ,&nbsp;Miyuki Uno ,&nbsp;Solange M.T. Serrano ,&nbsp;Roger Chammas ,&nbsp;André Zelanis","doi":"10.1016/j.jprot.2025.105597","DOIUrl":"10.1016/j.jprot.2025.105597","url":null,"abstract":"<div><div>Melanoma is an aggressive skin cancer with a high metastatic potential, influenced by both genetic and environmental factors. Proteases play a key role in shaping the tumor microenvironment and enabling transformed cells to actively colonize distant sites (metastasis). We performed proteomic mapping of protease cleavage sites in formalin-fixed paraffin-embedded tissue samples and profiled potentially active proteases in samples from melanoma patients with distinct prognostic outcomes. Although protein abundance alone did not indicate potential markers of disease progression, the observed cleaved fragments may serve for monitoring potentially active proteases in patient samples in targeted proteomics analysis. The findings provide valuable insights into melanoma biology and potential therapeutic prospects.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"325 ","pages":"Article 105597"},"PeriodicalIF":2.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic signatures in triple-negative breast cancer","authors":"Sohit Kashyap ,&nbsp;Vishal Patidar ,&nbsp;Anil Kumar ,&nbsp;Prachi Sahu ,&nbsp;Monisha Dhiman ,&nbsp;Pardeep Garg ,&nbsp;Aklank Jain ,&nbsp;Anjana Munshi","doi":"10.1016/j.jprot.2026.105598","DOIUrl":"10.1016/j.jprot.2026.105598","url":null,"abstract":"&lt;div&gt;&lt;div&gt;An aggressive and heterogeneous malignancy, referred to as triple-negative breast cancer, is characterised by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Treatment options remain limited, relying primarily on chemotherapy due to the lack of well-defined therapeutic targets, which is linked with poor prognosis and high recurrence rates. Proteomics and other high-throughput technologies have significantly advanced TNBC research by enabling the identification of protein-based biomarkers with potential applications in diagnosis, prognosis, and treatment. Through protein biomarkers that affect immune checkpoints, cell-surface glycoproteins, and regulators of tumor microenvironment interactions, key protein signatures from tumor tissue, serum, and exosomal proteomics have been found to have the potential to predict chemotherapy response and disease progression. To develop new therapeutic approaches, these biomarkers are being investigated. Combining proteomics with other omics technologies, such as transcriptomics and genomics, enables the development of precision medicine approaches and provides deeper insights into the pathophysiology of TNBC. Clinically validated and newly developed protein biomarkers for diagnosis, prognosis, and treatment interventions are described in this review. The molecular mechanistic aspects have also been discussed. These biomarkers have the potential to aid in the classification, risk stratification, and development of personalized treatment approaches for TNBC.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Significance statement&lt;/h3&gt;&lt;div&gt;Triple-negative breast cancer (TNBC) remains a highly aggressive and heterogeneous form of breast cancer, with very few treatment strategies. This review synthesizes past discoveries, current clinical applications, and future opportunities of proteomics in TNBC, making it highly relevant to the theme of this Special Issue on “Past, Present and Future of Proteomics.” By consolidating evidence from human and other preclinical studies, it highlights how proteomic signatures have already transformed our understanding of TNBC biology and subtype classification, while also outlining their growing impact as diagnostic, prognostic, and therapeutic markers.&lt;/div&gt;&lt;div&gt;Importantly, the review emphasizes the translational shift enabled by next-generation proteomic technologies to redefine precision medicine for TNBC. It showcases how proteomics can facilitate personalized medicine, drug repurposing, and rational combination therapies, and describes novel avenues such as single-cell proteomics and integrative immunoproteogenomics that are driving the field forward.&lt;/div&gt;&lt;div&gt;Thus, this work not only consolidates what has been achieved but also provides perspectives on emerging technologies and innovative applications that could revolutionize biomarker discovery and clinical management of TNBC. It highlights proteomics as a critical pillar in shaping the futu","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"325 ","pages":"Article 105598"},"PeriodicalIF":2.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145927329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emphasizing the importance of interactions and networks in proteomics","authors":"Jean Armengaud","doi":"10.1016/j.jprot.2026.105599","DOIUrl":"10.1016/j.jprot.2026.105599","url":null,"abstract":"","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"325 ","pages":"Article 105599"},"PeriodicalIF":2.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145985097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic comparison of human brain tissue preservation methods","authors":"Laura Plantera ,&nbsp;Anna Didio ,&nbsp;Uta Ceglarek ,&nbsp;Ingo Bechmann","doi":"10.1016/j.jprot.2025.105589","DOIUrl":"10.1016/j.jprot.2025.105589","url":null,"abstract":"<div><div>This study investigated the impact of tissue preservation methods on protein profiles analyzed by reversed-phase liquid chromatography-high-resolution mass spectrometry (LC-HRMS) using data-independent acquisition (DIA). Proteomic profiles from formalin-fixed, formalin-fixed and paraffin-embedded (FFPE), and fresh-frozen human brain tissues (cortex and hippocampus, <em>n</em> = 6) were compared, including an FFPE-specific protein extraction kit (<em>n</em> = 4).</div><div>Formalin-fixed samples more closely resembled fresh-frozen profiles than FFPE or FFPE-Kit samples, while still showing high correlation and overlap with FFPE tissues in principal component analyses. A core set of 1753 proteins was consistently detected across all sample preparation methods. A total of 35 proteins were identified exclusively in fresh-frozen samples, but without functional enrichment. Quantitative comparisons to the proteome of fresh-frozen tissue revealed an underrepresentation of cellular processes, energy metabolism, signaling, and transport related to protein properties such as length, location, and hydrophobicity. In contrast, neuronal development and phagosome-related pathways were overrepresented in fixed tissues.</div><div>In a pilot study comparing low (Braak 0-II, <em>n</em> = 4) and high (Braak IV-VI, n = 4) Alzheimer's disease (AD) stages using formalin-fixed samples, we identified 12 potential protein biomarkers, primarily nucleosomal proteins and carboxypeptidase M (CPM).</div><div>These findings suggest that formalin-fixed brain tissue provides reliable proteomic information, making it a valuable resource for neurodegenerative disease research.</div></div><div><h3>Significance</h3><div>Proteomics offers enormous potential for investigating the molecular regulation of the human brain. Valuable tissue samples are often preserved in formalin or additionally with paraffin for later analysis. The potential value of these preserved samples for proteomic analysis has already been recognized. However, tissue preservation poses a challenge for proteome analysis. Consequently, several studies have compared different protein extraction protocols for fixed samples. In addition, studies have been published comparing protein extraction from FFPE samples with fresh-frozen samples. To our knowledge, this is the first study to compare protein extraction across all three tissue preservation methods with subsequent functional analysis using samples obtained from the same donors, thereby eliminating inter-donor variability and enabling a direct comparison of preservation effects. This study validates a protein extraction protocol from formalin-fixed samples, laying the groundwork for future research into potential biomarkers in formalin-fixed samples.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"325 ","pages":"Article 105589"},"PeriodicalIF":2.8,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural diversity of lipid A modulates neutrophil proteome and secretome responses.","authors":"Jose R Pittaluga Villarreal, Doeun Kim, Sung Hwan Yoon, Vanya Bhushan, Jiraphorn Issara-Amphorn, Jacob Pederson, Nathan P Manes, Aleksandra Nita-Lazar","doi":"10.1016/j.jprot.2026.105643","DOIUrl":"10.1016/j.jprot.2026.105643","url":null,"abstract":"<p><p>Neutrophils (PMNs) are central effector cells of the innate immune system, deploying antimicrobial functions such as degranulation, ROS production, and release of antimicrobial mediators. However, the neutrophil reprogramming in response to structurally distinct lipopolysaccharide (LPS) stimuli remains incompletely defined. Here, we integrated functional profiling with quantitative high-resolution proteomics to compare human PMN responses to two LPS preparations differing primarily in lipid A acylation: hexaacylated LPS from Escherichia coli (ECO-LPS) and tetra-acylated LPS from Francisella tularensis (FT-LPS). Principal component analysis (PCA) revealed that inter-donor variability was the dominant source of variation. ECO-LPS induced clear activation phenotypes and robust, time-dependent proteome remodeling, including early loss of L-selectin and progressive depletion of granule-associated proteins concomitant with increased abundance of inflammatory signaling proteins. In contrast, FT-LPS treated PMNs were indistinguishable from controls at the cellular proteome level. In the secretome, ECO-LPS treatment caused enrichment of neutrophil degranulation and granule lumen components, consistent with intracellular depletion of granules. FT-LPS elicited limited secretory changes, suggesting a restrained activation or primed state without coordinated intracellular remodeling. Together, our results demonstrate that lipid A acylation is a key determinant of neutrophil activation state and provide a resource for defining proteomic signatures associated with LPS sensing. SIGNIFICANCE: Neutrophils are essential first- responder cells of the innate immune system, and their activation is classically studied using targeted sets of surface markers and functional readouts, while the proteome- and secretome-level dynamics remain less well defined. By applying quantitative DIA proteomics to both the intracellular proteome and the secretome of primary human neutrophils, this study reveals how lipid A structure dictates the depth and coordination of neutrophil activation. The data demonstrate that hexaacylated LPS drives coordinated depletion of degranulation-associated proteins with a concomitant appearance in the secretome. In contrast, tetra-acylated LPS fails to induce comparable intracellular remodeling and instead produces only subtle secretory responses consistent with restrained activation. These findings refine our mechanistic understanding of how structurally distinct endotoxins differentially regulate neutrophil effector functions, emphasize the donor-intrinsic proteomic variation, and provide a reference that can guide future studies of attenuated innate sensing and neutrophil-focused therapeutic approaches.</p>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":" ","pages":"105643"},"PeriodicalIF":2.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lunatin-1: A peptide derived from the venom of the Hadruroides lunatus scorpion modulates signaling pathways in HL60 tumor cells to induce cytotoxic effects","authors":"Edleusa M. Lima-Batista ,&nbsp;Diana Paola Gómez-Mendoza ,&nbsp;Maurício Nogueira Moysés ,&nbsp;Kamila de Sousa Gomes ,&nbsp;Brener Cunha Carvalho ,&nbsp;Maria Elena de Lima ,&nbsp;Elaine M. Souza-Fagundes ,&nbsp;Aristóbolo Mendes da Silva ,&nbsp;Frank Kjeldsen ,&nbsp;Thiago Verano-Braga ,&nbsp;Adriano M.C. Pimenta","doi":"10.1016/j.jprot.2025.105571","DOIUrl":"10.1016/j.jprot.2025.105571","url":null,"abstract":"<div><div>Lunatin-1 is a 13-residue cytotoxic peptide derived from the venom of the scorpion <em>Hadruroides lunatus</em>. This study investigated its early effects on cellular signaling in the human promyelocytic leukemia cell line HL-60 using integrated proteomics and phosphoproteomics. Lunatin-1 regulated key mediators of apoptosis, such as caspase-2 (CASP2) and MEK1 (MAP2K1), and impacted major signaling pathways such as MAPK and PI3K/AKT. Lunatin-1 induced caspase-dependent and -independent apoptotic signaling, reduced AKT1 phosphorylation, and promoted BAX activation, consistent with mitochondrial apoptosis. These findings demonstrate that Lunatin-1 disrupts pro-survival signaling and activates multiple cell death pathways, highlighting its potential as a therapeutic candidate for hematologic malignancies.</div></div><div><h3>Significance</h3><div>This study provides a comprehensive analysis of the early molecular events triggered by Lunatin-1, a venom-derived peptide, in HL60 leukemia cells. Through integrated proteomic and phosphoproteomic approaches, we reveal that Lunatin-1 disrupts key survival pathways, notably MAPK and PI3K/AKT, and activates both caspase-dependent and -independent mechanisms of apoptosis. The peptide modulates proteins involved in DNA damage response, cell cycle regulation, and oxidative stress, offering insight into its multifaceted cytotoxic effects. These findings advance our understanding of venom-derived peptides as potential anticancer agents and underscore Lunatin-1's therapeutic promise for targeting resistant cancer cell populations.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"324 ","pages":"Article 105571"},"PeriodicalIF":2.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145587862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MALDI Deamidation Score (MDS): A fast and flexible method for assessing deamidation in ZooMS data and its application to the Denisova Cave bone assemblage","authors":"Fei Yang ,&nbsp;Ismael Rodríguez Palomo ,&nbsp;Bharath Anila Bhuvanendran Nair ,&nbsp;Samantha Brown","doi":"10.1016/j.jprot.2025.105577","DOIUrl":"10.1016/j.jprot.2025.105577","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Estimating deamidation from ZooMS spectra has frequently been achieved using the q2e method due to its high-throughput capacity and ease of use. Despite this, q2e only works with spectral data in txt format, operates slowly, and employs a genetic algorithm for fitting, which is stochastic and less interpretable. Furthermore, q2e only estimates deamidation at the peptide level and does not generate a sample-wide summary. The introduction of the Parchment Glutamine Index (PQI) presented an alternative method. Initially designed for a large ZooMS dataset of parchment, it utilises weighted least squares and a linear mixed-effects model (LME) to generate a peptide deamidation estimation and a sample level index, respectively. To address the limitations of q2e and expand the applicability of PQI to a wider range of archaeological tissues and MALDI-TOF-derived data (such as ZooMS data on bone collagen), we developed the MALDI Deamidation Score (MDS), an iteration of the PQI method optimised for handling large-scale datasets. MDS is more streamlined for analysing multi-species data with customisable peptide lists, offering dramatically reduced processing time. Using the published Denisova Cave ZooMS assemblage, we demonstrate that different peptides exhibit varying deamidation patterns over time, making the use of a single peptide to represent overall deamidation potentially biased. Such information is invaluable for investigating key questions such as protein preservation and site formation processes.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Significance&lt;/h3&gt;&lt;div&gt;We introduce the MALDI Deamidation Score (MDS), a new model that estimates deamidation at both peptide and sample levels from MALDI-derived datasets. MDS streamlines multi-species analyses with customisable peptide lists and markedly reduces processing time, enabling robust and large-scale deamidation estimation. Before MDS, deamidation in ZooMS has often been inferred from a single peptide common to Eurasian terrestrial mammals. Applied to the published Denisova Cave ZooMS assemblage, MDS reveals peptide-specific temporal deamidation patterns, showing that single-peptide proxies can be biased as peptides differ in deamidation rates and may be subject to different taphonomic processes. These results have broad relevance for studies of protein preservation and site-formation processes related to molecular taphonomy across archaeological and paleontological contexts. Looking ahead, as MDS allows a customisable peptide list, it has the potential to extend deamidation analysis of ZooMS data beyond terrestrial mammals to marine mammals and non-mammalian vertebrates (e.g., birds), and to different proteinaceous material such as keratin. It also has the potential to be compatible with different instruments used in peptide mass fingerprinting, such as MALDI-TOF, MALDI-FTICR, and TIMS-TOF. We believe that MDS will contribute greatly to our understanding of deamidation on different peptide sequences under various e","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"324 ","pages":"Article 105577"},"PeriodicalIF":2.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145661494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal proteomic profiling of mouse kidney reveals dynamic responses to Crotalus durissus terrificus envenomation","authors":"Isabela de Oliveira Cavalcante Pimentel ,&nbsp;Wellington da Silva Santos ,&nbsp;Fabio Montoni ,&nbsp;Alison Felipe Alencar Chaves ,&nbsp;Rosangela Aparecida dos Santos Eichler ,&nbsp;Ismael Feitosa Lima ,&nbsp;Talita Souza-Siqueira ,&nbsp;Milton Yutaka Nishiyama-Jr ,&nbsp;Lilian de Jesus Oliveira ,&nbsp;Emer Suavinho Ferro ,&nbsp;Leo Kei Iwai","doi":"10.1016/j.jprot.2025.105574","DOIUrl":"10.1016/j.jprot.2025.105574","url":null,"abstract":"<div><div>Snakebite envenoming by <em>Crotalus durissus terrificus</em> causes significant morbidity, particularly acute kidney injury (AKI), though its molecular mechanisms remain poorly understood. This study provides the first comprehensive temporal proteomic atlas of renal responses to <em>C. d. terrificus</em> envenomation, combining TMT-based quantitative proteomics with multivariate bioinformatics and histopathological validation in a mouse model (0.5 LD50). We identified 2567 renal proteins, with 904 significantly altered (FDR ≤ 0.05), demonstrating a proteomic crisis that peaked at 12 h (400 increased, 451 decreased) and was already evident at 6 h (15 increased, 37 decreased). Changes at 1 h and 24 h were minimal at the single-protein level. These results delineate a precise biphasic progression: from acute phase at 6 h to 12 h, characterized by oxidative stress, mitochondrial dysfunction, and loss of key tubular transport proteins dominated by maladaptive repair and fibrotic signaling. Our temporal analysis defines distinct windows for intervention: an early opportunity for antioxidant therapy to counter acute injury, followed by a critical period where anti-fibrotic strategies are required to prevent the progression to irreversible kidney damage.</div></div><div><h3>Significance</h3><div>Snakebite envenomation by <em>Crotalus durissus terrificus</em> rattlesnake venom frequently leads to acute kidney injury (AKI), yet the molecular mechanisms driving nephrotoxicity remain poorly characterized. This study provides the first comprehensive temporal proteomic atlas of renal responses to envenomation, revealing that the most robust proteomic remodeling occurs between 6 h and 12 h, with hundreds of proteins significantly altered. These changes highlight mitochondrial dysfunction, oxidative stress, and tubular injury, exemplified by decrease of CUBN and AGT, alongside shifts in cytoskeletal and ribosomal pathways. Early (1 h) and late (24 h) effects were limited at the single-protein level and are reported as exploratory trends, such as NDRG2 (hypoxia response) and ITGA3 (fibrotic signaling). Histological validation confirmed progressive tubular damage and maladaptive repair, paralleling the proteomic signatures. Together, these findings delineate a critical window of maximal molecular disruption at 12 h, providing mechanistic insights into the progression from acute injury to maladaptive remodeling. The data suggest that therapeutic strategies targeting early oxidative stress (e.g., antioxidant interventions) or late fibrotic pathways (e.g., RAS modulation) could mitigate venom-induced damage. This work bridges molecular pathophysiology with clinical outcomes, informing future translational research.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"324 ","pages":"Article 105574"},"PeriodicalIF":2.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145634997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced proteome profiling of human cerebrospinal fluid using a commercial plasma enrichment strategy","authors":"Eva Borràs ,&nbsp;Federica Anastasi ,&nbsp;Olga Pastor ,&nbsp;Marc Suárez-Calvet ,&nbsp;Eduard Sabidó","doi":"10.1016/j.jprot.2025.105575","DOIUrl":"10.1016/j.jprot.2025.105575","url":null,"abstract":"<div><div>Cerebrospinal fluid (CSF) is a valuable liquid biopsy for identifying protein biomarkers in neurological diseases, yet its proteome profiling faces challenges due to the large dynamic range of protein abundances. In this study, we assessed the effectiveness of a commercial enrichment strategy, initially developed for plasma samples, in enhancing the detection of low-abundance proteins in human CSF. We demonstrate significant improvements in protein identification and coverage depth while maintaining high reproducibility and low coefficients of variation. These findings underscore the potential of this enrichment strategy to facilitate rapid and sensitive CSF analysis, advancing biomarker discovery in neurological research.</div></div><div><h3>Significance</h3><div>This article highlights the effectiveness of a commercial plasma enrichment strategy in enhancing the detection of low-abundance proteins in human CSF. The article shows improvements in proteome coverage and it underscores the potential of this strategy to facilitate rapid and sensitive CSF analysis.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"324 ","pages":"Article 105575"},"PeriodicalIF":2.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145610237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfur metabolism regulates endoplasmic reticulum stress survival through the interaction between cystathionine beta-synthase and Sec14 protein","authors":"Elias Nieto-Zaragoza ,&nbsp;Emilio Espinoza-Simón ,&nbsp;Damián Ramirez-Robles ,&nbsp;Emmanuel Ríos-Castro ,&nbsp;Ramiro Garza-Domínguez ,&nbsp;Francisco Torres-Quiroz","doi":"10.1016/j.jprot.2025.105573","DOIUrl":"10.1016/j.jprot.2025.105573","url":null,"abstract":"<div><div>The gasotransmitter hydrogen sulfide (H₂S) is implicated in a myriad of biological processes, including disease causing alterations. Besides acting as an antioxidant molecule, H₂S reacts with thiol groups from cysteine residues found in proteins. This post-translational modification (PTM), called S-persulfidation, plays an essential role during endoplasmic reticulum (ER) stress. Here we demonstrated that yeast cystathionine beta-synthase (Cys4), is the main responsible for ER H₂S-mediated homeostasis. We also found that during ER stress, Cys4 interacts with specific proteins that we identified with at least one cysteine residue modified by hydrogen sulfide. Finally, we focused on one interactor with reported tunicamycin sensitivity, the phospholipid transfer protein Sec14. In addition to Cys4 immunoprecipitation, we confirmed this interaction by pulling down Sec14 interactors. Deleting <em>CYS4</em> generated the accumulation of lipid droplets inside the cytosol, similar to Sec14. For the first time, we described a set of protein-protein interactions of Cys4 during ER stress with cysteines susceptible to S-persulfidation, leaving an open question about the role and regulation of the rest of the interactors.</div></div><div><h3>Significance</h3><div>In this study, we identified several interactor partners of yeast cystathionine beta synthase and analyzed cysteine residues with cysteine S-persulfidations. Although yeast have multiple H₂S producing enzymes, Cys4 seems to play a predominant role during ER stress. Temporal and spatial generation of H₂S is becoming significant in the field, and our findings contribute to that understanding. Besides, Cys4/Sec14 complex found here, seven different Cys4 complexes that may be regulated by H₂S were also reported. Because the biogenesis of this PMT is still controversial, findings like these support the hypothesis of interaction mediated biogenesis. H₂S producing enzymes specificity would help control their signaling across the cell. Finally, all Cys4 interactors with modified cysteines, including Sec14, are excellent targets to study how this PTM regulates enzyme functioning. Structural and functional assays with cysteine mutants in these proteins will shed light on new regulatory mechanisms.</div></div>","PeriodicalId":16891,"journal":{"name":"Journal of proteomics","volume":"324 ","pages":"Article 105573"},"PeriodicalIF":2.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}