Molecular & Cellular Proteomics最新文献

{"title":"Genetic Rescue of Disrupted Synaptic Protein Interaction Network Dynamics Following SYNGAP1 Reactivation.","authors":"Vera Stamenkovic, Felicia Harsh, Breann Kniffen, Gavin Rumbaugh, Stephen E P Smith","doi":"10.1016/j.mcpro.2026.101614","DOIUrl":"10.1016/j.mcpro.2026.101614","url":null,"abstract":"<p><p>Synaptic protein interaction networks (PINs) dynamically translate neural activity into biochemical signals that regulate synaptic structure and plasticity. Disruption of these coordinated networks is a common feature of autism spectrum disorder (ASD) risk genes, yet it remains unclear whether the molecular organization of a perturbed network can be restored after development. Here, we examined how post-developmental re-expression of the synaptic Ras GTPase-activating protein SynGAP1 affects network structure and signaling dynamics in a conditional SynGAP1 haploinsufficient mouse. Quantitative multiplex co-immunoprecipitation (QMI) across development revealed that SynGAP haploinsufficiency selectively reduced SynGAP-containing complexes without broadly disrupting NMDA-dependent network responses. Tamoxifen-inducible re-expression of SynGAP at postnatal day 21 fully restored both steady-state and activity-dependent interactions within the SynGAP module in hippocampus, and additionally normalized secondary alterations in Shank-Homer scaffolding complexes in somatosensory cortex. These data demonstrate that biochemical restoration of a disrupted synaptic network is achievable, even after early developmental windows have closed. Our findings suggest that while critical periods may constrain functional recovery, molecular network normalization remains possible through genetic reactivation of haploinsufficient synaptic regulators.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101614"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339351","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}

{"title":"Proteome Profiling Reveals NQO2 Activity Contributing to Proteasome Inhibitor Resistance in Multiple Myeloma Cell Lines.","authors":"Chien-Yun Lee, Seungbin Han, Larissa Haertle, Umair Munawar, Cornelia Vogt, Johanna Streubel, Andrej Besse, Lenka Besse, Christoph Driessen, Hermann Einsele, Johannes Waldschmidt, Martin Kortüm, Bernhard Kuster","doi":"10.1016/j.mcpro.2026.101615","DOIUrl":"10.1016/j.mcpro.2026.101615","url":null,"abstract":"<p><p>Proteasome inhibitors (PIs) are frontline therapies for multiple myeloma (MM). Although MM patients initially respond to PIs, resistance frequently emerges. While all PIs nominally target the same proteasomal catalytic subunit (PSMB5), the extent to which resistance mechanisms are the same or different among different PIs or between patients is poorly understood. To address this, we performed proteome and phosphoproteome profiling of 12 MM cell line models, comprising four parental lines (AMO-1, ARH77, L363, and RPMI8226) paired with lines that acquired resistance to bortezomib (BTZ) or carfilzomib (CFZ). Over 7000 proteins and up to 10,000 phosphopeptides were identified per cell line, enabling a comprehensive comparative analysis of shared and cell line-specific resistance signatures at the protein level. Data analysis revealed surprisingly few changes in the phosphoproteome but substantial reprogramming of the proteome in most models. Beyond known adaptations such as the overexpression of the PI target PSMB5 and the drug efflux transporter ABCB1, we identified the oxidoreductases NQO1 and NQO2 as significantly upregulated proteins under chronic proteotoxic stress across several models. Pharmacological follow up in PI resistant AMO-1 cells showed that NQO2 inhibition by imatinib fully restored CFZ sensitivity, validating NQO2 as a contributor to resistance formation in this model system.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101615"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148339330","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}

{"title":"Alovudine Targets mtDNA-dependent Proteins Encoded by Genes Recurrently Amplified in Metastatic Breast Cancer Cohorts.","authors":"Jessica Brandi, Gloria Gatto, Federica Sotgia, Michael P Lisanti, Daniela Cecconi","doi":"10.1016/j.mcpro.2026.101622","DOIUrl":"10.1016/j.mcpro.2026.101622","url":null,"abstract":"<p><p>Previously, we demonstrated that high levels of mitochondrial DNA (mtDNA) were functionally associated with \"stemness\" and aggressive phenotypic behaviors in human breast cancer cells, including spontaneous metastasis. More specifically, we showed that treatment with Alovudine induced mtDNA-depletion in MDA-MB-231 cells and prevented their ability to form colonies in vitro and metastasize in vivo. To better understand the underlying mechanism(s) and identify candidate mtDNA-dependent mitochondrial protein biomarkers relevant to metastatic breast cancer, Alovudine-treated MDA-MB-231 cells were subjected to proteomics analysis. For comparison purposes, mtDNA-depleted cells (MDA-MB-231 and MCF-7) were generated and also subjected to proteomics analysis. Intersection of these three distinct data sets revealed that a small number of proteins were commonly downregulated in mtDNA-depleted cells and Alovudine-treated cells. Remarkably, many of these nuclear-encoded mitochondrial genes (>20) exhibited recurrent genomic amplification across metastatic breast cancer cohorts. Therefore, the action of a single drug, namely Alovudine, was sufficient to effectively suppress the expression of a large number of mitochondrial proteins associated with i) gene amplification and ii) cancer cell metastasis, in human breast cancer patients. These findings may have important clinical implications for the development of new therapeutics targeting advanced breast cancer.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101622"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13486814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148447967","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}

{"title":"Integrated Multi-Omics Analysis Uncovers Molecular Dysregulation in Glucosylceramide Synthase-Deficient Human Induced Pluripotent Stem Cells.","authors":"Julia Beimdiek, Karsten Cirksena, Charlotte Rossdam, Smilla Brand-Merseburger, Astrid Oberbeck, Philippe V Barbosa, Ana Tzvetkova, Malte Juchem, Christian Bär, Thomas Thum, Axel Schambach, Andreas Pich, Britta Brügger, Andreas W Kuss, Falk F R Buettner","doi":"10.1016/j.mcpro.2026.101630","DOIUrl":"10.1016/j.mcpro.2026.101630","url":null,"abstract":"<p><p>Glycosphingolipids are membrane lipids characterized by highly diverse glycosylation patterns. They are involved in numerous cellular processes and can be linked to diseases. With the aim to investigate their role in early mammalian developmental processes in vitro, we knocked out the UDP-glucose ceramide glucosyltransferase gene (UGCG) encoding the enzyme glucosylceramide synthase (UGCG) in human induced pluripotent stem cells (hiPSCs) by CRISPR/Cas9. The functional impairment of UGCG was confirmed by glycomic profiling. UGCG KO hiPSCs displayed normal morphology, growth behavior, and expression of stem cell markers compared to WT hiPSCs. Furthermore, the KO cells maintained pluripotency, as evidenced by their capacity for in vitro differentiation into all three embryonic germ layers and their ability to form teratomas in vivo. Quantitative proteomic analysis of explanted teratoma derived from WT and UGCG KO hiPSCs revealed differential expression of numerous proteins, with notable enrichment of pathways associated with signal transduction or protein localization and transport. Phosphorylation profiling of key kinases and their targets uncovered reduced activation of STAT family transcription factors in UGCG KO hiPSCs. Complementary transcriptomic profiling combined with Ingenuity Pathway Analysis of differentially expressed genes between WT and UGCG KO hiPSCs, as well as their ectodermal derivatives, revealed a predicted positive enrichment of proteins associated with signaling pathways in UGCG KO hiPSCs. Global lipidomic profiling showed a significant increase in sphingomyelin levels in UGCG KO hiPSCs and their ectodermally differentiated derivatives, whereas total ceramide content remained comparable between UGCG KO and WT cells. In summary, despite the absence of overt phenotypic changes, our findings demonstrate that glycosphingolipid deficiency induces multiple molecular perturbations in hiPSCs.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101630"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13520899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579364","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}

{"title":"\"If the Shoe Fits?\"-Benchmarking Plasma Proteomic Sample-Preparation Workflows Across Human and Rat Biofluids.","authors":"Samantha J Emery-Corbin, Joel R Steele, Dylan H Multari, Erwin Tanuwidjaya, Iresha Hanchapola, Komagal Kannan Sivaraman, Han-Chung Lee, Scott A Blundell, Idrish Ali, Terence J O'Brien, Pouya Faridi, Ralf B Schittenhelm","doi":"10.1016/j.mcpro.2026.101626","DOIUrl":"10.1016/j.mcpro.2026.101626","url":null,"abstract":"<p><p>The push for new clinical biomarkers has seen rapid innovation in biofluid analysis, particularly for plasma. For mass-spectrometry (MS)-based analysis, achieving depth and quantitative accuracy whilst ensuring throughput continues to shape plasma methods development. Numerous workflows have emerged that mitigate high-abundance suppression and expand dynamic range, especially when paired with next-generation MS instrumentation. Yet systematic evaluations that also consider biological variables (e.g., biofluid type, species) and technical parameters (e.g., MS methods) are limited. Here, we benchmarked eight sample-preparation workflows spanning neat approaches (SP3, STrap), depletion (perchloric acid, PerCA), and corona-enrichment strategies (MagNet HILIC/SAX, Enrich-iST, ProteoNano). We compared their performance across human plasma, human serum, and rat plasma, analyzing all samples on an Orbitrap Astral (Thermo) using two plasma-optimized data-independent acquisition (DIA) methods: one discovery-maximized and one throughput-maximized. We identified 2726 human and 3767 rat proteins across workflows and methods, including ∼1000 from neat plasma. Increasing throughput incurred a ∼20 to 30% reduction in depth, depending on workflow and species. EV-enrichment produced the deepest proteomes but with distinct compositions relative to neat, depleted, and secreted-protein-enriched samples, revealing a unique sub-proteome niche. Several workflows also performed markedly better in rat plasma, supporting improved sensitivity for preclinical analyses. Enrichment or depletion dramatically reshaped the balance of tissue- and cell-specific proteins detectable in plasma, suggesting that workflow choice should be guided by the organs, immune targets, or inflammatory signals most relevant to the study. In this vein, statistical analysis of differentially abundant proteins showed that >90% of detected proteins were significantly altered between workflows, with the largest numbers arising from the corona-enrichment strategies, underscoring how strongly workflow choice shapes the downstream proteome. Taken together, these findings emphasize a rapidly expanding plasma methodological landscape, where the most effective workflow is the one most precisely tailored to a cohort's biology.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101626"},"PeriodicalIF":6.3,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13488069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148497780","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}

{"title":"Temporal Proteomic Characterization of SARS-CoV-2-Infected Mouse Lungs.","authors":"Geun Hee Han, Misol Do, Dain On, Haengdueng Jeong, Jeong Jin Kim, Dohyun Han, Dongyoon Shin, Kyunggon Kim, Jung Seon Seo, Sung-Hee Kim, Jiseon Kim, Donghun Jeon, Hyuna Noh, Suhyeon Yoon, Sang Gyu Lee, Hyo-Jung Lee, Hong Bin Kim, Manki Song, Man-Seong Park, Kang-Seuk Choi, Jun Won Park, Jun-Won Yun, Jeon-Soo Shin, Ho-Young Lee, Hyuk Wan Ko, Jun-Young Seo, Ki Taek Nam, Daehee Hwang, Youngsoo Kim, Je Kyung Seong","doi":"10.1016/j.mcpro.2026.101618","DOIUrl":"10.1016/j.mcpro.2026.101618","url":null,"abstract":"<p><p>Understanding dynamic activations of pathophysiological processes in the infected lungs is important for effective treatment of SARS-CoV-2 infection. Time-course transcriptome analyses of infected lungs have been performed to address this issue. Since proteins actually execute the pathophysiological processes, however, the time-course transcriptome data provide limited information regarding their temporal transitions. Here, we present time-course proteomic profiling of lung tissues from K18-hACE2 transgenic mice using liquid chromatography-tandem mass spectrometry analysis at day 0, 1, 2, 5, and 7 after SARS-CoV-2 infection. Clustering analysis to identify early, intermediate, and late up-regulated proteins, analysis of pathways enriched by these proteins, and network analysis of early, intermediate, and late upregulated pathways revealed detailed dynamic activations of molecular networks perturbed upon infection, and further proposed five markers that represented early-to-intermediate activation of nonsense-mediated decay (Smg6 and Upf1), intermediate-to-late activation of phagocytosis (Fcgr4 and Lamp2), and late activation of neutrophil extracellular trap formation (Padi4) that could be associated with severe pathological transitions. Immunohistochemistry analysis confirmed these temporal upregulation patterns of the five markers identified from the time-course proteome data, and immunofluorescence analysis further confirmed that Padi4 was up-regulated predominantly in neutrophils at the late stage. Our temporal proteomic analysis suggests potential pathways and molecule markers that can be used to predict severe pathological transitions during the course of SARS-CoV-2 infection.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101618"},"PeriodicalIF":6.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13697281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376416","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}

{"title":"Proteome-wide Ubiquitinome Profiling Reveals Substrate-specific Dynamics Within the USP7 Network.","authors":"Joyce Wolf van der Meer, Jan A van der Knaap, Ayestha Sijm, Karel Bezstarosti, Dick H W Dekkers, Wouter A S Doff, Jeroen A A Demmers, C Peter Verrijzer","doi":"10.1016/j.mcpro.2026.101602","DOIUrl":"10.1016/j.mcpro.2026.101602","url":null,"abstract":"<p><p>USP7 is a pleiotropic deubiquitylating enzyme that is involved in tumor suppression, (neuro) development, chromatin regulation and the DNA damage response. How USP7 regulates these diverse pathways is still unclear. Here, we report data-independent acquisition and label free quantitation mass spectrometry to profile the proteome-wide impact of USP7 on substrate de-ubiquitylation and overall protein abundance. First, we identified proteins associated with endogenous USP7 by immunopurification followed by data-independent acquisition and label free quantitation mass spectrometry. Integration of our new results with earlier interactomes of epitope-tagged USP7 yielded a consensus set of high-confidence protein targets. Domain mapping analysis revealed that, in addition to the TRAF domain, the ubiquitin-like domains of USP7 play a key role in substrate selection. Using specific enrichment of tryptic K-ε-GG peptides, we mapped proteome-wide changes in ubiquitinome dynamics following inhibition of USP7. Combining unbiased proteome-wide and targeted quantitative mass spectrometry revealed that deubiquitylation by USP7 can have different effects on the stability of distinct substrates, and suggests that USP7's activity profile is substrate-dependent rather than an intrinsic enzymatic property. Thus, in addition to providing a proteome-wide map of USP7 target sites, our multi-angle proteomics approach reveals that the effects of USP7-mediated deubiquitylation on its targets are remarkably variable and substrate-specific. Finally, based on these detailed molecular insights we show how USP7 connects various neurodevelopmental syndromes and tumor suppression pathways.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101602"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265234","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}

{"title":"A Parallel Accumulation-Mobility Aligned Fragmentation Strategy Utilizing High-Resolution Ion Mobility for High-Performance Proteomics Analysis.","authors":"Leonard C Rorrer, Liulin Deng, Lauren Royer, Isabel Uribe, Benjamin C Orsburn, Oliver Bernhardt, Tejas Gandhi, Lukas Reiter, Daniel DeBord","doi":"10.1016/j.mcpro.2026.101608","DOIUrl":"10.1016/j.mcpro.2026.101608","url":null,"abstract":"<p><p>Here we present a novel data-independent acquisition (DIA) mass spectrometry (MS) operating mode termed parallel accumulation-mobility aligned fragmentation (PAMAF) that offers enhanced speed and sensitivity of ion fragmentation analysis for discovery workflows such as bottom-up proteomics. This mode of operation leverages high-resolution ion mobility (HRIM) separation capabilities of the structures for lossless ion manipulation technology to achieve HRIM-based precursor isolation in place of traditional quadrupole filtering approaches. PAMAF mode increases the number of features that can be identified per MS1/MS2 acquisition cycle by employing mobility-based time alignment to associate fragment ions with their corresponding precursor ions. By using a high-speed, lossless separation technique for precursor isolation instead of the comparatively slow and wasteful quadrupole filtering, ion losses are avoided while simultaneously increasing the rate at which precursor ions are sequentially fragmented and detected. In addition, by accumulating ions while the previous packet of ions is being analyzed, the PAMAF mode achieves ∼100% ion utilization efficiency. Benchmarking results of LC-PAMAF-MS analysis of a whole cell protein digest showed ∼6× more protein group identifications compared to a standard data-dependent acquisition analysis without HRIM on the same QTOF instrument, and >100 x improvement for low-load workflows. Quantitative evaluations demonstrated that PAMAF mode could quantify low abundance peptides, including those undetectable by data-dependent acquisition. In addition, since precursor isolation in PAMAF mode is size-based rather than m/z-based, coeluting isobars and isomers can be resolved prior to fragmentation, eliminating chimeric spectra that compromise identification accuracy. We also explored the benefits of combining HRIM and quadrupole isolation to achieve improved specificity termed DIA-PAMAF mode, which enabled the detection of over 8000 protein groups from a HeLa digest analysis. PAMAF mode brings a powerful new technique to the field of proteomics with the potential to improve the sensitivity and selectivity of mass spectrometry-based proteomics.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101608"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302468","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}

{"title":"Plasma Proteomic Profiling Was Used to Discover a Biochemical Recurrence Prediction Model for Prostate Cancer.","authors":"Ning Xu, Linhui Zhang, Zhenmei Yao, Liqing Li, Maoping Cai, Yunzhi Wang, Xihao Wang, Subei Tan, Kai Li, Jiacheng Lyu, Hongkai Wang, Zhaoyu Qin, Jinwen Feng, Bo Dai, Yao Zhu, Hang Xiang, Xiaojian Qin, Guowen Lin, Yanzi Gu, Fei Ding, Jianyuan Zhao, Yuanyuan Qu, Chen Ding, Dingwei Ye, Wenjun Yang","doi":"10.1016/j.mcpro.2026.101568","DOIUrl":"10.1016/j.mcpro.2026.101568","url":null,"abstract":"<p><p>Prostate cancer (PCa) is one of the most common malignancies in men. There is limited data available regarding potential minimally-invasive biomarkers for predicting PCa outcomes and disease monitoring. Here, we investigate the proteomic profile of plasma in 222 patients with PCa and 159 healthy controls. Integrative analyses of the proteome profile and clinical features identified protein networks related to International Society of Urological Pathology (ISUP) grades and prostate-specific antigen (PSA). Proteome-based classification revealed three subtypes, PCa-I, PCa-II, and PCa-III, reflecting distinct clinical prognosis and molecular signatures. We develop a 17-protein panel and established a biochemical recurrence prediction model that effectively predicts biochemical recurrence for patients with PCa, which is better than ISUP grades and pathological stages. Finally, we validate the protein panel by parallel reaction monitoring (PRM) assay in an independent cohort. Collectively, this study portrays the plasma proteomic landscape of PCa cohort and provides a comprehensive resource for further biological and predictive research in PCa.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101568"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13321017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691180","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}

{"title":"Long-Chain S-Acylation Is a Key Modulator During the Macrophage Inflammatory Response.","authors":"Anneroos E Nederstigt, Samiksha Sardana, Francine Rodrigues Ianiski, Marc P Baggelaar","doi":"10.1016/j.mcpro.2026.101600","DOIUrl":"10.1016/j.mcpro.2026.101600","url":null,"abstract":"<p><p>Long-chain S-acylation is a reversible lipid modification critical for regulating protein localization, stability, and signaling, yet its role in macrophage-mediated inflammation remains incompletely understood. Here, we combine stable isotope labeling by amino acids in cell culture (SILAC) with site-specific acyl-biotin exchange (ssABE) to generate a comprehensive map of the long-chain S-acylation landscape in THP-1 macrophages polarized to M0 and M(LPS + IFNɣ) states. Our quantitative proteomics reveal polarization-specific S-acylation patterns and uncover numerous inflammation-related modification sites, including novel S-acyl-peptidoforms, which are distinct S-acylated variants of the same peptide such as WARS (C305/C309), highlighting their potential relevance in macrophage activation. Pharmacological inhibition of S-acylation with the broad-spectrum inhibitor 2-bromopalmitate suppresses secretion of key pro-inflammatory chemokines (CXCL9, CXCL10, and CCL4) and disrupts IDO1-mediated tryptophan catabolism, while Palmostatin B mainly stabilizes S-acylation on GPCR signaling proteins. Together, these findings position long-chain S-acylation as a key regulatory mechanism during macrophage activation and a promising target for therapeutic intervention in inflammatory disease.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101600"},"PeriodicalIF":6.3,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13380729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148218521","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}