Molecular & Cellular Proteomics最新文献

{"title":"Whole blood proteome dynamics defines predictive diagnostic and prognostic signatures of cryptococcal infection.","authors":"Michael Woods, Jason A McAlister, Lauren Segeren, Mayara Silva, Jared Deyarmin, Amirmansoor Hakimi, Daniel Hermanson, Jana Richter, Stephanie N Samra, Jennifer Geddes-McAlister","doi":"10.1016/j.mcpro.2025.101083","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101083","url":null,"abstract":"<p><p>Across the globe, fungi are impacting the lives of millions of people through the development of infections ranging from superficial to systemic with limited treatment options. To effectively combat fungal disease, rapid and reliable diagnostic methods are required, including current methodologies using antigen detection, culturing, microscopy, and molecular tools. However, the flexibility of these platforms to diagnose infection using non-invasive methods and predict the outcome of disease are limited. In this study, we apply state-of-the-art mass spectrometry-based proteomics to perform dual perspective (i.e., host and pathogen) profiling of cryptococcal infection. Whole blood collected over a temporal scale following murine model challenged with the human fungal pathogen, Cryptococcus neoformans, detected >3,000 host proteins and 160 fungal proteins. From the host perspective, temporal regulation of known immune-associated proteins, including eosinophil peroxidase and lipocalin-2, along with suppression of lipoproteins, demonstrated infection- and time-dependent host remodeling. Conversely, from the pathogen perspective, known and putative virulence-associated proteins were detected, including proteins associated with fungal extracellular vesicles and host immune modulation. We also observed and validated a new mechanism of immune system response to C. neoformans through modulation of haptoglobin. Further, we assessed the predictive power of dual perspective proteome profiling toward prognostics of cryptococcal infection and report a previously undisclosed integration among virulence factor production, immune system modulation, and individual model survival. Together, our findings pose novel biomarkers of cryptococcal infection from whole blood and highlight the potential of personal proteome profiles to determine the prognosis of cryptococcal infection, a new parameter in fungal disease management.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101083"},"PeriodicalIF":5.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251846","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":"Comparative N-Glycoproteomics Reveals Subtype-Specific N-Glycosylation Signatures and Immune Associations in Cholangiocarcinoma.","authors":"Zhili Xia, Li Gao, Meng Hu, Yingjie Li, Kexin Yu, Ningzu Jiang, Long Gao, Yu Liu, Ying Lu, Yanxian Ren, Chenjun Tian, Yawen Lu, Jindu Zhang, Haiying Yu, Ping Yue, Yanyan Lin, Rou Zhang, Yanqiu Gong, Wenbo Meng","doi":"10.1016/j.mcpro.2025.101084","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101084","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) comprises intrahepatic (iCCA) and extrahepatic (eCCA) subtypes, each exhibiting distinct molecular characteristics. Understanding these differences is critical for identifying subtype-specific therapeutic targets and advancing precision medicine. Protein glycosylation, a key post-translational modification, regulates immune evasion and metastasis, yet the glycoproteomic difference between iCCA and eCCA remains unexplored. Here we presented the first comprehensive N-glycoproteomic profile of eCCA and compared it with iCCA using a publicly available dataset. Our N-glycoproteomic analysis of paired eCCA tumors and normal adjacent tissues (NATs) identified 8,372 N-glycopeptides, 3,467 N-glycosites, and 2,627 N-glycoproteins. Comparative analysis revealed distinct N-glycosylation signature, with eCCA exhibiting higher fucosylated glycans and iCCA showing increased sialylation. Pathway enrichment analysis of N-glycoproteins revealed a more prominent lysosome-related enrichment in eCCA, whereas pathways related to immune modulation, cytoskeletal components, and the extracellular matrix were significantly enriched in both subtypes. Immune profiling revealed an immunosuppressive microenvironment in both eCCA and iCCA, characterized by reduced natural killer cell infiltration and subtype-specific fibroblast and endothelial cell remodeling. DPM1, a glycosylation enzyme highly expressed in eCCA, was associated with tumor-specific N-glycopeptides and reduced immune cell infiltration. Its knockdown impaired cell migration, and glycoproteomic analysis implicated DPM1 in regulating adhesion, proteostasis, and immune pathways, highlighting its potential as a therapeutic target in eCCA. Our findings provide insights into N-glycosylation alterations in CCA subtypes, underscoring N-glycosylation-related mechanisms as potential biomarkers and therapeutic targets, particularly in eCCA.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101084"},"PeriodicalIF":5.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251888","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 analysis of human topoisomerases reveals their distinct and diverse cellular functions.","authors":"Huimin Zhang, Yun Xiong, Zhen Chen, Junjie Chen","doi":"10.1016/j.mcpro.2025.101082","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101082","url":null,"abstract":"<p><p>Topoisomerases are essential for resolving topological stress in DNA during key cellular processes. In human cells, six topoisomerases perform specialized yet overlapping functions to manage these challenges. To investigate their distinct and shared roles, as well as their involvement in DNA damage repair, we conducted a comprehensive analysis of the human topoisomerase-associated protein landscape. Using tandem affinity purification coupled with mass spectrometry, we mapped the protein-protein interaction networks of five human topoisomerases under both normal and stressed conditions. Our analysis identified several key interactions that may regulate topoisomerase function. Notably, TOP1 interacts with PUM3, which undergoes a similar relocalization from nucleoli to nucleoplasm following treatment with a TOP1 poison. Additionally, we uncovered novel interactions of TOP3A with NSMCE4A, YTHDC2, and NDUFAF7, as well as a previously uncharacterized interaction between TOP3B and the mitochondrial membrane protein TDRKH (TDRD2). We further examined dynamic changes in these interactomes in response to TOP1 and TOP2 poisons and replication stress, distinguishing between interactions in chromatin and soluble fractions. These findings provide new insights into the regulation and functional coordination of human topoisomerases, offering potential biomarkers or therapeutic targets for topoisomerase inhibitors in cancer treatment.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101082"},"PeriodicalIF":5.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225741","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":"Breaking Boundaries in Histone Modification MS-based Detection: A Tailored Search Strategy for Unrestricted identification of novel epigenetic marks.","authors":"Alessandro Vai, Roberta Noberini, Andrea Graziadei, Daniel A Polasky, Fengchao Yu, Alexey I Nesvizhskii, Tiziana Bonaldi","doi":"10.1016/j.mcpro.2025.101080","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101080","url":null,"abstract":"<p><p>Histone post-translational modifications (PTMs) play a crucial role in regulating gene expression and maintaining DNA integrity, and their aberrations are linked to various diseases, including cancer. While lysine acetylation and methylation have been extensively studied, recent research has uncovered additional PTMs that significantly contribute to chromatin structure and function. Mass spectrometry (MS) is the most effective analytical method for studying histone PTMs; however, computational limitations often restrict the analysis to common modifications. Unrestrictive search strategies have the potential to enable a more comprehensive characterization of the histone modification landscape. In this work, we systematically assess the application of unrestrictive search approaches to histone data. After evaluating the limitations of these methods, we develop a novel bioinformatics workflow, named HiP-Frag (Histone PTM analysis with FragPipe), which enables the identification of 96 sites decorated with uncommon PTMs on core histones-60 of which were previously unreported-as well as 55 histone marks on linker histones, including 13 novel ones, purified from human cell lines and primary samples. The expanded histone PTM analysis enabled by this strategy is among the first to extract previously unexplored epigenetic information from MS raw data. This approach paves the way for a facilitated and more streamlined identification of uncommon and yet unannotated histone modifications, supporting a deeper dissection of the histone code and the understanding of the potential biological role of the novel epigenetic marks.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101080"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213245","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":"Proteogenomic Reassessment Provides Novel Insight into the Life Cycle of Tetrahymena thermophila.","authors":"Chen Gu, Mingkun Yang, Jing Zhang, GuangYing Wang, Lu Fu, Kai Chen, Lujuan Li, Peng Zhang, Shuai Luo, Fangdian Yang, Jiao Zhan, Wei Miao, Feng Ge, Jie Xiong","doi":"10.1016/j.mcpro.2025.101081","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101081","url":null,"abstract":"<p><p>Tetrahymena thermophila (T. thermophila), a well-established model organism, has been instrumental in advancing our understanding of evolutionarily conserved biological processes. A key biological feature of this unicellular eukaryote is its life cycle strategy, marked by three major stages: growth, starvation and conjugation. Despite its prominence as a model system, functional genomic studies of T. thermophila have been constrained by limitations in the accuracy and completeness of gene discovery since the initial genome assembly in 2006. To address this gap, we performed a multi-stage proteogenomic analysis, combining genomic sequencing with high-resolution mass spectrometry (MS)-based proteomic profiling across ten strategically selected life cycle states. This integrative approach enabled a comprehensive reassessment of gene discovery, leading to the validation of 24,319 previously predicted protein-coding genes and the identification of 383 novel genes. Additionally, our investigation systematically identified a diverse repertoire of post-translational modifications (PTMs), including 7,123 modification sites distributed across 4,705 proteins. These PTMs are postulated to exert critical regulatory functions during developmental phase transitions. Collectively, this work not only refines the T. thermophila gene catalog and enhances its utility as a robust genetic toolkit for advancing biological research but also offers new mechanistic insights into the molecular regulation of its life cycle progression. Keywords: Tetrahymena thermophila; proteogenomics; mass spectrometry; genome assessment; post-translational modification.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101081"},"PeriodicalIF":5.5,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213219","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":"High accuracy stool biomarkers of pre-cancerous colorectal cancer identified using a 2000-plex immunoproteomic screen.","authors":"Kamala Vanarsa, Jessica Castillo, Hao Li, Kala T Pham, Maria Akter, Sravya Gude, Kyung Hyun Lee, Claudia Pedroza, Robert Bresalier, Nicholas Chia, Chandra Mohan","doi":"10.1016/j.mcpro.2025.101079","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101079","url":null,"abstract":"<p><strong>Background: </strong>Given the morbidity and mortality associated with colorectal cancer, novel biomarkers are clearly warranted, especially for early detection METHOD: An antibody-based screen of 2000 proteins was utilized to identify stool proteins that were elevated in patients with CRC, compared to healthy controls (HCs). 37 lead candidates were selected for ELISA validation in three independent cohorts comprised of CRC patients, advanced adenoma patients, and healthy controls, drawn from two different ethnicities.</p><p><strong>Results: </strong>Of the 2000 proteins interrogated, 116 were differentially expressed in CRC stool, with 45 being elevated at 2-fold or higher; 37 of these proteins were selected for ELISA validation in 3 independent patient cohorts. Stool MMP-8, MMP-9, Hemoglobin, PGRP-S, Haptoglobin, and Fibrinogen emerged as being most discriminatory for distinguishing CRC from healthy controls (AUC: 0.91-0.95), across cohorts and ethnicities, with several of these being significantly higher in more advanced stages of CRC. Stool Fibrinogen, MMP-9, Hemoglobin, MMP-8, and PGRP-S were the top 5 stool proteins with the highest accuracy for distinguishing advanced adenoma from HC, with stool Fibrinogen topping the list with a diagnostic accuracy of 0.86. Functional pathway analysis revealed a significant over-representation of pathways related to anti-oxidant activity, integrin/receptor binding, cytokines, blood coagulation, and lipoprotein biosynthesis in patients with CRC compared to HC. Nuclear Factor IC (NFIC) and IKZF2 were identified as key regulators of the molecular cascades over-represented in CRC.</p><p><strong>Conclusion: </strong>Stool Fibrinogen, MMP-8, MMP-9, PGRP-S, Haptoglobin, and Myeloperoxidase emerge as promising biomarkers for distinguishing CRC/advanced adenomas/healthy stools, meeting or outperforming current yardsticks.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101079"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206860","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":"Chasing the Ghost Proteome in the Dark matter.","authors":"Tristan Cardon, Isabelle Fournier, Michel Salzet","doi":"10.1016/j.mcpro.2025.101076","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101076","url":null,"abstract":"<p><p>Emerging evidence shows that translation from non-canonical open reading frames (ORFs) produces a diverse set of biologically active proteins. These ORFs reside in 5' and 3' untranslated regions, long non-coding RNAs, overlapping frames within annotated genes (dual coding), pseudogenes, and can initiate at non-AUG start codons. The resulting products, variously termed microproteins, small proteins (smPROTs), small ORF-encoded peptides (SEPs), and alternative proteins (AltProts), modulate fundamental cellular processes, including metabolic flux and epigenetic regulation. We consolidate these entities under the umbrella of the ghost proteome, a functional proteome arising from the genome's presumed \"dark matter.\" This concept is distinct from the dark proteome, which refers to regions of canonical proteins lacking structural, functional, or experimental annotation and is not necessarily derived from non-canonical loci. Recognizing the ghost proteome expands the boundary of what is considered protein-coding, demands harmonized nomenclature and database integration, and motivates systematic discovery and functional characterization. By reframing sequences once dismissed as non-coding or \"junk,\" the ghost proteome compels a re-evaluation of genome annotation and reveals new opportunities to interrogate biology and disease.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101076"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206832","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":"Zscan4 as a candidate conveyor of early developmental defects in O-GlcNAc transferase intellectual disability.","authors":"Veronica M Pravata, Hao Jiang, Andrew T Ferenbach, Angus Lamond, Daan M F van Aalten","doi":"10.1016/j.mcpro.2025.101077","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101077","url":null,"abstract":"<p><p>Variants in the human β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) gene give rise to an intellectual disability (ID) syndrome termed OGT congenital disorder of glycosylation (OGT-CDG). The mechanisms by which loss of OGT and/or protein O-GlcNAcylation lead to this syndrome are not understood, but symptoms associated with the syndrome suggest a developmental origin. Here, we establish and characterise two lines of mouse embryonic stem cells carrying different patient mutations and show that these mutations lead to disrupted O-GlcNAc homeostasis. Using quantitative proteomics on these cells in the pluripotent state, we identify candidate proteins/pathways that could underpin this syndrome. In addition to the increased levels of OGT and decreased levels of OGA reflecting disrupted O-GlcNAc homeostasis, we find that expression of the ID gene Zscan4 is upregulated. This is associated with increased levels of the OGT:Ten Eleven (Tet) - protein complex that regulates DNA methylation and Zscan4 expression. These data uncover a potential mechanism contributing to the developmental aspects of OGT-CDG.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101077"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206850","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 portrait of degranulation program in human circulating neutrophils upon multi-inflammatory and infectious activation.","authors":"Ying Hua, Ziqi Zhou, Can Zhang, Hai Fang, Mingxing Wu, Zhiyong Chen, Xin Ku, Wei Yan","doi":"10.1016/j.mcpro.2025.101078","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101078","url":null,"abstract":"<p><p>Neutrophils respond rapidly to inflammation and infection via defense mechanisms, including degranulation, reactive oxygen species (ROS) production, and neutrophil extracellular trap (NET) formation (known as 'NETosis'). As the most abundant neutrophil components, granule proteins constitute the major mediators of neutrophil effector functions and likely orchestrate their functional diversity. However, a systematic profile of these proteins, particularly their temporal release dynamics during inflammatory responses, remains uncharacterized. Here, we performed a 'multi-state' proteomic study to explore circulating neutrophils' dynamic responses to diverse infectious and inflammatory signals over time. Circulating neutrophils exhibited both conserved and stimulus-specific protein expression programs. Through integrated characterization of the cellular and secretory proteome landscapes, we delineated the release patterns of canonical granule proteins and identified inflammatory mediators, including soluble membrane receptors. Notably, granule membrane receptors were translocated to the cell surface and shed via proteolytic cleavage, highlighting their dynamic regulation and diversity. These findings revealed complexity of the neutrophil degranulation program, demonstrating its stimulus-dependent and temporally layered nature. Our study provides a functional atlas of neutrophil degranulation upon inflammation, which would strengthen our understanding on the neutrophil activation in inflammation and facilitating the exploration of inflammation management therapies.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101078"},"PeriodicalIF":5.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206858","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":"Spinal cord phosphoproteome of SCA2 mouse model reveals alteration of ATXN2-N-term PRM-SH3-actin interactome and of autophagy.","authors":"Luis-Enrique Almaguer-Mederos, Arvind Reddy Kandi, Nesli-Ece Sen, Júlia Canet-Pons, Luca-Malena Berger, Matthew P Stokes, Kathryn Abell, Jana Key, Suzana Gispert, Georg Auburger","doi":"10.1016/j.mcpro.2025.101072","DOIUrl":"https://doi.org/10.1016/j.mcpro.2025.101072","url":null,"abstract":"<p><p>Toxic polyglutamine (polyQ) expansions in ATXN2 trigger neurodegenerative processes, causing Spinocerebellar Ataxia type 2 (SCA2), and enhancing TDP-43-dependent pathology in Amyotrophic Lateral Sclerosis (ALS) / Fronto-Temporal Dementia (FTD). Primary disease events can be compensated transiently, delaying disease manifestation. To define potential therapy targets, here we studied how cells modify phosphoprotein signals, using preferentially affected nervous tissue from end-stage Atxn2-CAG100-KnockIn mice. The spinal cord phosphoproteome revealed massive hyperphosphorylations flanking the polyQ expansion in ATXN2 and for SQSTM1, and moderate hyperphosphorylations also for ALS proteins OPTN, UBQLN2, TNIP1 and TBK1-targeted TAX1BP1. Conversely, strong hypophosphorylations of WNK1, SPARCL1 and PSMD9 were found. Significant enrichments of SH3-containing proteins, autophagy / endocytosis factors, and actin modulators could be explained by N-terminal, polyQ-adjacent, proline-rich motifs (PRM) in ATXN2, suggesting that SCA2 pathogenesis is highly similar to Huntington's disease where neurotoxicity is mediated by abnormal polyQ-PRM-SH3 interactions. Validation of protein and mRNA levels were done in mouse spinal cord, and embryonic fibroblasts or patient fibroblasts after bafilomycin or arsenite treatment, observing polyQ-dependent OPTN deficiency and SQSTM1 induction impairment. Overall, this phosphoproteome profile identified and quantified the main cellular efforts in adapting autophagy pathways to the aggregation propensity of the ATXN2-N-term.</p>","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"101072"},"PeriodicalIF":5.5,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137556","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}