Journal of Proteome Research最新文献

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Elucidating Interactome Dynamics of the A2A Adenosine Receptor in the Presence of Polydeoxyribonucleotide. 多脱氧核糖核苷酸存在下A2A腺苷受体相互作用动力学的研究。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-09 DOI: 10.1021/acs.jproteome.4c00782
Wonseok Lee, Ahrum Son, Jaeho Ji, Eunjeong Han, Ja-Young Cho, Ju-Won Kim, Young-Ok Kim, Hee Jeong Kong, Hyunsoo Kim
{"title":"Elucidating Interactome Dynamics of the A2A Adenosine Receptor in the Presence of Polydeoxyribonucleotide.","authors":"Wonseok Lee, Ahrum Son, Jaeho Ji, Eunjeong Han, Ja-Young Cho, Ju-Won Kim, Young-Ok Kim, Hee Jeong Kong, Hyunsoo Kim","doi":"10.1021/acs.jproteome.4c00782","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00782","url":null,"abstract":"<p><p>Polydeoxyribonucleotide (PDRN) is a tissue regeneration substance that resembles human DNA and is present in mammalian cells. It stimulates physiological regeneration and metabolic activity, and the effects of PDRN are attributed to the activation of Adenosine A2A receptors (ADORA2A). Several previous studies have demonstrated that PDRN activates ADORA2A, which has been shown with various models including rat fibroblasts, human umbilical vein endothelial cells (HUVECs), and the experimental autoimmune uveitis (EAU) model, resulting in the upregulation of angiogenesis and growth factor. In this work, we primarily used HUVECs to study the overall changes and dynamics of proteins related to their ADORA2A activation. We conducted selected reaction monitoring-mass spectrometry (SRM-MS), and we founded 374 proteins and 193 peptides demonstrating both upregulation and downregulation in expression. We conducted gene ontology (GO) analysis and physical network analysis and discovered novel networks and indirect interactions of proteins related to neuronal differentiation among the ADORA2A-associated protein. Finally, using the AlphaFold multimer, we were able to predict interaction sites among ADORA2A-associated proteins in the network associated with neuronal cell differentiation. Specifically, we predicted five interaction sites between ADORA2A and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), forming the edge. Thus, we provided indicators for further research using ADORA2A present in a robust network and highlighted the potential of PDRN to impact neuronal differentiation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598918","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}
引用次数: 0
Mass Spectrometry Reveals Novel Features of Tubulin Polyglutamylation in the Flagellum of Trypanosoma brucei. 质谱分析揭示了布鲁氏锥虫鞭毛微管蛋白多谷氨酰化的新特征。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-09 DOI: 10.1021/acs.jproteome.5c00107
Marija Nisavic, Thibault Chaze, Serge Bonnefoy, Carsten Janke, Philippe Bastin, Mariette Matondo, Julia Chamot-Rooke
{"title":"Mass Spectrometry Reveals Novel Features of Tubulin Polyglutamylation in the Flagellum of <i>Trypanosoma brucei</i>.","authors":"Marija Nisavic, Thibault Chaze, Serge Bonnefoy, Carsten Janke, Philippe Bastin, Mariette Matondo, Julia Chamot-Rooke","doi":"10.1021/acs.jproteome.5c00107","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00107","url":null,"abstract":"<p><p>Tubulin polyglutamylation is a key feature of eukaryotic cilia and flagella that is essential for their function. The diversity of enzymes catalyzing polyglutamylation with different specificities inspired the hypothesis of the tubulin code. In the protist parasite <i>Trypanosoma brucei</i>, nine different glutamylase enzymes are potentially involved in tubulin glutamylation. To decipher the trypanosome tubulin code generated by this diversity, we aimed at determining tubulin glutamylation patterns by robust mass spectrometry (MS)-based proteomics. MS approaches exist for many post-translational modifications but none for the chemically complex polyglutamylation. We therefore optimized a nanoLC-MS/MS pipeline from sample preparation to data analysis using synthetic peptides for quantification. Our approach enabled the quantification of C-terminal tubulin peptides with up to 11 supplementary glutamates on α-, and five on β-tubulin from the flagellum of <i>T. brucei</i>. In addition to the known E445 on α- and E435 on β-, a novel glutamylation site of β-tubulin was discovered at E438. Furthermore, our data revealed an increase in enzymatic detyrosination with increasing length of the glutamate chains, especially for α-tubulin. This indicates cross-talk between the modifications and different detyrosination rates of the two tubulin types. Our efficient analytical pipeline advances understanding of the tubulin code in <i>T. brucei</i>.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598919","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}
引用次数: 0
Decoding the Impact of Isolation Window Selection and QuantUMS Filtering in DIA-NN for DIA Quantification of Peptides and Proteins. 解码DIA- nn中隔离窗选择和量子滤波对多肽和蛋白质DIA定量的影响。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-08 DOI: 10.1021/acs.jproteome.5c00009
Jorge da Cruz Moschem, Bianca Carla Silva Campitelli de Barros, Solange Maria de Toledo Serrano, Alison Felipe Alencar Chaves
{"title":"Decoding the Impact of Isolation Window Selection and QuantUMS Filtering in DIA-NN for DIA Quantification of Peptides and Proteins.","authors":"Jorge da Cruz Moschem, Bianca Carla Silva Campitelli de Barros, Solange Maria de Toledo Serrano, Alison Felipe Alencar Chaves","doi":"10.1021/acs.jproteome.5c00009","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00009","url":null,"abstract":"<p><p>Proteomic studies using data-independent acquisition (DIA) have gained momentum in all fields of biology. Search engines are evolving to keep up with the latest developments in instrument technology. DIA-NN is the most popular software for DIA analysis under an academic use license. The QuantUMS algorithm in DIA-NN improves quantification quality control by calculating three scores (protein group MaxLFQ quality, empirical quality, and quantity quality) that assess the agreement between MS1 and MS2 features. Here, we show that applying specific cutoffs to these scores can significantly impact the results. To enable you to make a more informed decision about what represents a reasonable trade-off (identification and quantification), we evaluated the impact of different combinations of the scores on data acquired using different isolation windows and a mixture of two species with a known ratio. To test consistency and reproducibility across the six different versions of DIA-NN, we compared them and found high reproducibility except for version 1.9. We show that filtering by QuantUMS scores removes proteins with low abundances and high coefficients of variation. Finally, we developed the QC4DIANN Shiny application in the R language for interactive quality control automation.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590059","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}
引用次数: 0
Mitochondria-Derived Reactive Oxygen Species Regulation of Tardigrade Osmobiosis Revealed by Proteomics of Hypsibius exemplaris. 线粒体来源的活性氧对缓步动物渗透作用的调控研究
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-07 DOI: 10.1021/acs.jproteome.5c00222
Evan R Stair, Brendin B Flinn, Aaron C Grimmett, Samantha J Balboa, Adam J Burr, Jessica A Siebold, Andrea Granados Baca, Meredith H Daughtridge, Derrick R J Kolling, Leslie M Hicks
{"title":"Mitochondria-Derived Reactive Oxygen Species Regulation of Tardigrade Osmobiosis Revealed by Proteomics of <i>Hypsibius exemplaris</i>.","authors":"Evan R Stair, Brendin B Flinn, Aaron C Grimmett, Samantha J Balboa, Adam J Burr, Jessica A Siebold, Andrea Granados Baca, Meredith H Daughtridge, Derrick R J Kolling, Leslie M Hicks","doi":"10.1021/acs.jproteome.5c00222","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00222","url":null,"abstract":"<p><p>Tardigrades are microscopic invertebrates renowned for their ability to survive extreme environmental stress such as radiation, extreme temperatures, and desiccation. Yet, the biochemical mechanisms they utilize to survive these extremes are poorly understood. Herein, we implement proteomics to investigate the biomolecular underpinnings of tardigrade osmobiosis - a survival state in response to osmotic pressure. Using two solutes, sucrose and NaCl, we reveal that de novo gene expression is not required for osmobiosis induction. While sucrose and NaCl induce slightly different proteomic effects, both solutes lead to an increased abundance or oxidation of proteins involved in ER or mitochondrial activity. Further, we investigate the role of mitochondrial reactive oxygen species (ROS) in tardigrade osmobiosis and demonstrate that inhibition of the alternative oxidase (AOX) within the mitochondrial respiratory chain (MRC) increases the rate of osmobiosis formation with both sucrose and NaCl. Subsequent electron paramagnetic resonance (EPR) spectroscopy reveals an increased rate of ROS formation in osmobiotes with AOX inhibited. Finally, inhibition of mitochondrial ROS significantly decreases the rate of osmobiote formation suggesting a regulation of osmobiosis through MRC-derived ROS. In sum, this work suggests mitochondrial-ROS signaling is necessary for tardigrade osmobiosis and further clarifies the biochemical mechanisms contributing to tardigrade extremotolerance.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582646","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}
引用次数: 0
Identifying Links between Alzheimer's Disease and Type 2 Diabetes through Proteomics. 通过蛋白质组学确定阿尔茨海默病和2型糖尿病之间的联系。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-07 DOI: 10.1021/acs.jproteome.5c00404
Tong N Chen, Adam L Orr, Anna G Orr, Nathaniel M Vacanti
{"title":"Identifying Links between Alzheimer's Disease and Type 2 Diabetes through Proteomics.","authors":"Tong N Chen, Adam L Orr, Anna G Orr, Nathaniel M Vacanti","doi":"10.1021/acs.jproteome.5c00404","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00404","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and type 2 diabetes (T2D) are both amyloidogenic, age-associated chronic diseases and their occurrences are linked by epidemiological evidence and common dysregulated molecular functions including glucose hypometabolism, dyslipidemias, and altered insulin signaling. High-throughput molecular profiling of the genome and transcriptome has advanced our understanding of their molecular links; however, proteomic signatures may reveal novel biomarkers and additional insights because proteins are the primary purveyors of molecular function. Herein, the contributions to our understanding of the molecular links between AD and T2D by high-throughput proteomics are reviewed. Collectively, the studies highlight strong, but broad, common molecular and metabolic signatures; however, more investigation is needed to define shared mechanisms and identify robust biomarkers and potential therapeutic targets.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574460","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}
引用次数: 0
Longitudinal Proteomic Changes in HCT 116 Colon Cancer Spheroids During Growth. HCT 116结肠癌球体生长过程中的纵向蛋白质组学变化。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-07 DOI: 10.1021/acs.jproteome.5c00207
Catherine B Whitney, Nicole C Beller, Brian D Fries, Arbil Lopez, Amanda B Hummon
{"title":"Longitudinal Proteomic Changes in HCT 116 Colon Cancer Spheroids During Growth.","authors":"Catherine B Whitney, Nicole C Beller, Brian D Fries, Arbil Lopez, Amanda B Hummon","doi":"10.1021/acs.jproteome.5c00207","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00207","url":null,"abstract":"<p><p>The FDA Modernization Act 2.0 permits data from advanced microphysiological systems, such as spheroids, to be used as a testbed for drug candidates entering phase 1 clinical trials. Despite their increasing adoption, spheroids of varying growth durations are often used interchangeably as disease models. While transcriptomic studies have been employed to monitor spheroids over time, proteomics has primarily been used to validate their utility as model systems and assess drug responses rather than for longitudinal studies. Here, we apply data independent acquisition with gas phase fractionation (DIA-GPF) proteomics to investigate temporal changes in HCT 116 spheroids every 2 days throughout 18 days of growth, identifying 6,835 proteins across all samples. Differential expression analysis reveals that day 2 spheroids more closely resemble monolayer cells than spheroids cultured for extended periods. Gene ontology (GO) term analysis of differentially expressed proteins indicates that relative to monolayer cells DNA replication is downregulated, while glycolysis is upregulated during spheroid maturation. Parallel reaction monitoring (PRM) experiments targeting thymidylate synthase and fructose-bisphosphate aldolase C validate the initial proteomic findings and corroborate the trends observed in the GO term analysis. These results highlight the importance of growth duration when spheroids are used as a model for avascular tumors.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574461","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}
引用次数: 0
ProMix: Enhancing Protein Quantification through Experimental Design and Statistical Normalization. ProMix:通过实验设计和统计归一化增强蛋白质定量。
IF 3.6 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-07 DOI: 10.1021/acs.jproteome.4c01108
Huaying Fang, Mei-Chiung Shih, Lihua Jiang, Felipe da Veiga Leprevost, Ruiqi Jian, Alexey I Nesvizhskii, Michael P Snyder, Hua Tang
{"title":"ProMix: Enhancing Protein Quantification through Experimental Design and Statistical Normalization.","authors":"Huaying Fang, Mei-Chiung Shih, Lihua Jiang, Felipe da Veiga Leprevost, Ruiqi Jian, Alexey I Nesvizhskii, Michael P Snyder, Hua Tang","doi":"10.1021/acs.jproteome.4c01108","DOIUrl":"10.1021/acs.jproteome.4c01108","url":null,"abstract":"<p><p>Isobaric labeling of biospecimens followed by mass spectrometry (MS) has become the method of choice for large-scale, untargeted, quantitative proteomic profiling. However, subtle variation in experimental conditions can amplify sample variability and introduce systematic biases. Motivated by the challenges and opportunities arose in a recent proteogenomic study, we developed ProMix, a flexible analytical framework designed to improve protein normalization by leveraging two key experimental design features: (1) the inclusion of an additional reference sample to serve as an internal standard, and (2) the incorporation of replicates of each specimen. ProMix can utilize either or both features. Through applications to both simulated and real data sets, we demonstrate the improved performance of ProMix and highlight the advantages of the enhanced experimental design strategies.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574463","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}
引用次数: 0
Machine Learning and DIA Proteomics Reveal New Insights into Carbapenem Resistance Mechanisms in Klebsiella pneumoniae. 机器学习和DIA蛋白质组学揭示肺炎克雷伯菌碳青霉烯耐药机制的新见解。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-07 DOI: 10.1021/acs.jproteome.5c00142
Guibin Wang, Ling Cao, Lingli Lian, Yuqian Wang, Juanqi Lian, Ziqiu Liu, Wenzhe Chen, Meichao Ji, Lanqing Gong, Lishan Zhang, Liping Li, Xiangmin Lin
{"title":"Machine Learning and DIA Proteomics Reveal New Insights into Carbapenem Resistance Mechanisms in <i>Klebsiella pneumoniae</i>.","authors":"Guibin Wang, Ling Cao, Lingli Lian, Yuqian Wang, Juanqi Lian, Ziqiu Liu, Wenzhe Chen, Meichao Ji, Lanqing Gong, Lishan Zhang, Liping Li, Xiangmin Lin","doi":"10.1021/acs.jproteome.5c00142","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00142","url":null,"abstract":"<p><p>The emergence of Carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) represents a major public health concern, primarily driven by its ability to evade a wide range of antibiotics. Despite extensive genomic studies, proteomic insights into antibiotic resistance mechanisms remain scarce. Here, we employed a Data-Independent Acquisition (DIA)-based quantitative proteomics approach to investigate proteomic differences between 78 CRKP and 18 Carbapenem-sensitive <i>K. pneumoniae</i> (CSKP) clinical isolates. A total of 3380 proteins were identified, with 946 showing significant differential expression. CRKP isolates exhibited increased expression of efflux pumps, beta-lactamases, and transcriptional regulators, while proteins associated with transport were enriched in CSKP isolates. To validate our findings, a quantitative proteomics analysis in an independent cohort of 10 CRKP and 11 CSKP isolates was performed. The key biomarkers identified via machine learning in the discovery cohort, including aldehyde dehydrogenase (KPN_03361), acyltransferase (KPN_02072), uncharacterized protein (YjeJ), plasmid partition protein B (ParaB), HTH-type transcriptional activator (RhaR), and beta-lactamase (Bla), were evaluated. They collectively achieved AUC > 0.7 in the validation cohort, confirming their discriminatory capacity as diagnostic markers. These findings provide novel insights into the molecular mechanisms of antibiotic resistance and identify promising biomarkers for diagnosing carbapenem-resistant <i>K. pneumoniae</i>, offering potential avenues for therapeutic intervention.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574462","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}
引用次数: 0
Integrative Phosphoproteomic and Proteomic Analysis of Candida albicans Exposed to Oxidative Stress. 氧化应激下白色念珠菌的综合磷酸化蛋白质组学和蛋白质组学分析。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-04 Epub Date: 2025-06-02 DOI: 10.1021/acs.jproteome.5c00137
Víctor Arribas, Ana Borrajo, María Luisa Hernáez, Raquel Martínez, Lucía Monteoliva, Concha Gil, Gloria Molero
{"title":"Integrative Phosphoproteomic and Proteomic Analysis of <i>Candida albicans</i> Exposed to Oxidative Stress.","authors":"Víctor Arribas, Ana Borrajo, María Luisa Hernáez, Raquel Martínez, Lucía Monteoliva, Concha Gil, Gloria Molero","doi":"10.1021/acs.jproteome.5c00137","DOIUrl":"10.1021/acs.jproteome.5c00137","url":null,"abstract":"<p><p><i>Candida albicans</i> is an opportunistic pathogen, which has recently been included in the high-priority list of pathogenic fungi by the World Health Organization (WHO). The scarce arsenal available to treat such invasive fungal infections makes the discovery of new antifungal targets an important task. This study utilizes DDA-MS technology to investigate both the phosphoproteomics and proteomics of <i>C. albicans</i> during its late-stage response to oxidative stress induced by H<sub>2</sub>O<sub>2</sub>, aiming to identify key proteins involved. Phosphorylation, as an important post-translational modification, plays a crucial role in the ability of <i>C. albicans</i> to survive oxidative stress. Our study enabled the identification and quantification of important changes in both protein abundance and phosphorylation events across multiple proteins following a 200 min 10 mM H<sub>2</sub>O<sub>2</sub> treatment. The use of the DDA-MS approach allowed for the identification of new actors in the response to oxidative stress. Novel phosphorylation sites were identified in kinases and transcription factors. Regarding protein kinases, Cdc5-reduced phosphorylation may mediate a transient G2 cell cycle arrest, while Kis1─the regulatory β-subunit of Snf1 kinase─might play a role in ROS scavenging following oxidative stress. In terms of transcription factors, Gzf3-decreased phosphorylation was essential for cell survival and ROS detoxification after oxidative stress.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"3484-3497"},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Metabolic Effects of Cellular Necrosis Caused by Exfoliative Toxin C (ExhC) from Mammaliicoccus sciuri. 哺乳弧菌剥脱毒素C (ExhC)引起细胞坏死的代谢作用。
IF 3.8 2区 生物学
Journal of Proteome Research Pub Date : 2025-07-04 Epub Date: 2025-05-22 DOI: 10.1021/acs.jproteome.4c01029
Carolina Gismene, Fábio Rogério de Moraes, Anelize Bauermeister, Thyerre Santana Da Costa, Marilia de Freitas Calmon, Luís Eduardo de Almeida Passos Cerbino, Paula Rahal, Rejane Maira Góes, Luiz Alberto Beraldo de Moraes, Ljubica Tasic, Raghuvir Krishnaswamy Arni
{"title":"Metabolic Effects of Cellular Necrosis Caused by Exfoliative Toxin C (ExhC) from <i>Mammaliicoccus sciuri</i>.","authors":"Carolina Gismene, Fábio Rogério de Moraes, Anelize Bauermeister, Thyerre Santana Da Costa, Marilia de Freitas Calmon, Luís Eduardo de Almeida Passos Cerbino, Paula Rahal, Rejane Maira Góes, Luiz Alberto Beraldo de Moraes, Ljubica Tasic, Raghuvir Krishnaswamy Arni","doi":"10.1021/acs.jproteome.4c01029","DOIUrl":"10.1021/acs.jproteome.4c01029","url":null,"abstract":"<p><p>Exfoliative toxins (ETs) are glutamyl endopeptidases (GEPs) belonging to the chymotrypsin-like serine protease family (CLSPs), and they play crucial roles in diverse skin diseases. Specifically, exfoliative toxin C (ExhC), expressed by <i>Mammaliicoccus sciuri</i>, is an atypical CLSP and has been classified as a moonlighting protein due to its ability to induce necrosis in specific cell lines, inhibit the phagocytic activity of macrophages, and cause skin exfoliation in pigs and mice. The latter function is attributed to the high specificity of ExhC for porcine and murine desmoglein-1, a cadherin that contributes to cell-cell adhesion within the epidermis. Although the amino acid residues responsible for ExhC-induced necrosis have been identified, the specific cellular metabolic pathways leading to cell death remain unclear. Herein, we employed nuclear magnetic resonance (NMR) and mass spectrometry (MS) to explore the metabolic pathways affected by the necrotic activity of ExhC in the BHK-21 cell line. The metabolic profile of cells exposed to subtoxic doses of ExhC revealed significant alterations in oxidative stress protection, energy production, and gene expression pathways. The data demonstrate the potential mechanisms of action of ExhC and highlight that this toxin causes cellular damage, even at low concentrations.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"3261-3271"},"PeriodicalIF":3.8,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12235709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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