Journal of Proteome Research最新文献_第6页

MALDI MSI Protocol for Spatial Bottom-Up Proteomics at Single-Cell Resolution. 用于单细胞分辨率空间自下而上蛋白质组学的 MALDI MSI 协议。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-24 DOI: 10.1021/acs.jproteome.4c00528

Andrej Grgic, Eva Cuypers, Ludwig J Dubois, Shane R Ellis, Ron M A Heeren

{"title":"MALDI MSI Protocol for Spatial Bottom-Up Proteomics at Single-Cell Resolution.","authors":"Andrej Grgic, Eva Cuypers, Ludwig J Dubois, Shane R Ellis, Ron M A Heeren","doi":"10.1021/acs.jproteome.4c00528","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00528","url":null,"abstract":"Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) started with spatial mapping of peptides and proteins. Since then, numerous bottom-up protocols have been developed. However, achievable spatial resolution and sample preparation with many wet steps hindered the development of single cell-level workflows for bottom-up spatial proteomics. This study presents a protocol optimized for MALDI-MSI measurements of single cells within the context of their 2D culture. Sublimation of CHCA, followed by a dip in ice-cold ammonium phosphate monobasic (AmP), produced peptide-rich mass spectra while maintaining matrix crystal sizes around 400 nm. This enables MALDI-MSI imaging of proteins in single cells grown on an ITO slide with a throughput of approximately 7800 cells per day. 89 peptide-like features corresponding to a single MDA-MB-231 breast cancer cell were detected. Furthermore, by combining the MALDI-MSI data with LC-MS/MS data obtained on cell pellets, we have successfully identified 24 peptides corresponding to 17 proteins, including actin, vimentin, and transgelin-2.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491151","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

Amino Acid Metabolism Subtypes in Neuroblastoma Identifying Distinct Prognosis and Therapeutic Vulnerabilities. 神经母细胞瘤的氨基酸代谢亚型识别不同的预后和治疗弱点

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-23 DOI: 10.1021/acs.jproteome.4c00554

Xing Zhou, Zhaokai Zhou, Xiaohan Qin, Jian Cheng, Yongcheng Fu, Yuanyuan Wang, Jingyue Wang, Pan Qin, Da Zhang

{"title":"Amino Acid Metabolism Subtypes in Neuroblastoma Identifying Distinct Prognosis and Therapeutic Vulnerabilities.","authors":"Xing Zhou, Zhaokai Zhou, Xiaohan Qin, Jian Cheng, Yongcheng Fu, Yuanyuan Wang, Jingyue Wang, Pan Qin, Da Zhang","doi":"10.1021/acs.jproteome.4c00554","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00554","url":null,"abstract":"Although amino acid (AA) metabolism is linked to tumor progression and could serve as an attractive intervention target, its association with neuroblastoma (NB) is unknown. Based on AA metabolism-related genes, we established three NB subtypes associated with distinct prognoses and specific functions, with C1 and C2 having better outcomes. The C1 displayed enhanced metabolic activity and recruited metabolism-associated cells. The C2 exhibited an activated immune microenvironment and was more vulnerable to immunotherapy. The C3, characterized by cell cycle peculiarity, possessed a dismal prognosis and high frequency of gene mutations and was susceptible to chemotherapy. Furthermore, single-cell RNA sequencing analysis revealed that the C3-associated Scissor+ cell subpopulation was characterized by notorious functional states and orchestrated an immunosuppressive microenvironment. Additionally, we identified that ALK and BIRC5 contributed to the shorter lifespan of C3 and their corresponding inhibitors were potential interventions. In conclusion, we identified three distinct subtypes of NB, which help us foster individualized therapeutic strategies to improve the prognosis of NB.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491145","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

In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease 对结直肠癌患者石蜡包埋组织样本的深入蛋白质组分析发现 TXNDC17 和 SLC8A1 是与疾病相关的关键蛋白质

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-23 DOI: 10.1021/acs.jproteome.3c0074910.1021/acs.jproteome.3c00749

Ana Montero-Calle*, María Garranzo-Asensio, Carmen Poves, Rodrigo Sanz, Jana Dziakova, Alberto Peláez-García, Vivian de los Ríos, Javier Martinez-Useros, María Jesús Fernández-Aceñero and Rodrigo Barderas*,

{"title":"In-Depth Proteomic Analysis of Paraffin-Embedded Tissue Samples from Colorectal Cancer Patients Revealed TXNDC17 and SLC8A1 as Key Proteins Associated with the Disease","authors":"Ana Montero-Calle*, María Garranzo-Asensio, Carmen Poves, Rodrigo Sanz, Jana Dziakova, Alberto Peláez-García, Vivian de los Ríos, Javier Martinez-Useros, María Jesús Fernández-Aceñero and Rodrigo Barderas*, ","doi":"10.1021/acs.jproteome.3c0074910.1021/acs.jproteome.3c00749","DOIUrl":"https://doi.org/10.1021/acs.jproteome.3c00749https://doi.org/10.1021/acs.jproteome.3c00749","url":null,"abstract":"A deeper understanding of colorectal cancer (CRC) biology would help to identify specific early diagnostic markers. Here, we conducted quantitative proteomics on FFPE healthy, adenoma, and adenocarcinoma tissue samples from six stage I sporadic CRC patients to identify dysregulated proteins during early CRC development. Two independent quantitative 10-plex TMT experiments were separately performed. After protein extraction, trypsin digestion, and labeling, proteins were identified and quantified by using a Q Exactive mass spectrometer. A total of 2681 proteins were identified and quantified after data analysis and bioinformatics with MaxQuant and the R program. Among them, 284 and 280 proteins showed significant upregulation and downregulation (expression ratio ≥1.5 or ≤0.67, p-value ≤0.05), respectively, in adenoma and/or adenocarcinoma compared to healthy tissue. Ten dysregulated proteins were selected to study their role in CRC by WB, IHC, TMA, and ELISA using tissue and plasma samples from CRC patients, individuals with premalignant colorectal lesions (adenomas), and healthy individuals. In vitro loss-of-function cell-based assays and in vivo experiments using three CRC cell lines with different metastatic properties assessed the important roles of SLC8A1 and TXNDC17 in CRC and liver metastasis. Additionally, SLC8A1 and TXNDC17 protein levels in plasma possessed the diagnostic ability of early CRC stages.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560484","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

Detection and Quantification of Drug–Protein Adducts in Human Liver 人体肝脏中药物蛋白加合物的检测和定量

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-23 DOI: 10.1021/acs.jproteome.4c0066310.1021/acs.jproteome.4c00663

Alex Zelter, Michael Riffle, David D. Shteynberg, Guo Zhong, Ellen B. Riddle, Michael R. Hoopmann, Daniel Jaschob, Robert L. Moritz, Trisha N. Davis, Michael J. MacCoss and Nina Isoherranen*,

{"title":"Detection and Quantification of Drug–Protein Adducts in Human Liver","authors":"Alex Zelter, Michael Riffle, David D. Shteynberg, Guo Zhong, Ellen B. Riddle, Michael R. Hoopmann, Daniel Jaschob, Robert L. Moritz, Trisha N. Davis, Michael J. MacCoss and Nina Isoherranen*, ","doi":"10.1021/acs.jproteome.4c0066310.1021/acs.jproteome.4c00663","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00663https://doi.org/10.1021/acs.jproteome.4c00663","url":null,"abstract":"Covalent protein adducts formed by drugs or their reactive metabolites are risk factors for adverse reactions, and inactivation of cytochrome P450 (CYP) enzymes. Characterization of drug–protein adducts is limited due to lack of methods identifying and quantifying covalent adducts in complex matrices. This study presents a workflow that combines data-dependent and data-independent acquisition (DDA and DIA) based liquid chromatography with tandem mass spectrometry (LC-MS/MS) to detect very low abundance adducts resulting from CYP mediated drug metabolism in human liver microsomes (HLMs). HLMs were incubated with raloxifene as a model compound and adducts were detected in 78 proteins, including CYP3A and CYP2C family enzymes. Experiments with recombinant CYP3A and CYP2C enzymes confirmed adduct formation in all CYPs tested, including CYPs not subject to time-dependent inhibition by raloxifene. These data suggest adducts can be benign. DIA analysis showed variable adduct abundance in many peptides between livers, but no concomitant decrease of unadducted peptides. This study sets a new standard for adduct detection in complex samples, offering insights into the human adductome resulting from reactive metabolite exposure. The methodology presented will aid mechanistic studies to identify, quantify and differentiate between adducts that result in adverse drug reactions and those that are benign.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571088","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

Introducing Molecular Hypernetworks for Discovery in Multidimensional Metabolomics Data 引入分子超网络以发现多维代谢组学数据

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-22 DOI: 10.1021/acs.jproteome.3c0063410.1021/acs.jproteome.3c00634

Sean M. Colby, Madelyn R. Shapiro, Andy Lin, Aivett Bilbao, Corey D. Broeckling, Emilie Purvine and Cliff A. Joslyn*,

{"title":"Introducing Molecular Hypernetworks for Discovery in Multidimensional Metabolomics Data","authors":"Sean M. Colby, Madelyn R. Shapiro, Andy Lin, Aivett Bilbao, Corey D. Broeckling, Emilie Purvine and Cliff A. Joslyn*, ","doi":"10.1021/acs.jproteome.3c0063410.1021/acs.jproteome.3c00634","DOIUrl":"https://doi.org/10.1021/acs.jproteome.3c00634https://doi.org/10.1021/acs.jproteome.3c00634","url":null,"abstract":"Orthogonal separations of data from high-resolution mass spectrometry can provide insight into sample composition and address challenges of complete annotation of molecules in untargeted metabolomics. “Molecular networks” (MNs), as used in the Global Natural Products Social Molecular Networking platform, are a prominent strategy for exploring and visualizing molecular relationships and improving annotation. MNs are mathematical graphs showing the relationships between measured multidimensional data features. MNs also show promise for using network science algorithms to automatically identify targets for annotation candidates and to dereplicate features associated with a single molecular identity. This paper introduces “molecular hypernetworks” (MHNs) as more complex MN models able to natively represent multiway relationships among observations. Compared to MNs, MHNs can more parsimoniously represent the inherent complexity present among groups of observations, initially supporting improved exploratory data analysis and visualization. MHNs also promise to increase confidence in annotation propagation, for both human and analytical processing. We first illustrate MHNs with simple examples, and build them from liquid chromatography- and ion mobility spectrometry-separated MS data. We then describe a method to construct MHNs directly from existing MNs as their “clique reconstructions”, demonstrating their utility by comparing examples of previously published graph-based MNs to their respective MHNs.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571021","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

Distinct Regions within SAP25 Recruit O-Linked Glycosylation, DNA Demethylation, and Ubiquitin Ligase and Hydrolase Activities to the Sin3/HDAC Complex SAP25中的不同区域为Sin3/HDAC复合物提供O-连接糖基化、DNA去甲基化、泛素连接酶和水解酶活性

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-22 DOI: 10.1021/acs.jproteome.4c0049810.1021/acs.jproteome.4c00498

Pratik Goswami, Charles A.S. Banks, Janet Thornton, Bethany D. Bengs, Mihaela E. Sardiu, Laurence Florens and Michael P. Washburn*,

{"title":"Distinct Regions within SAP25 Recruit O-Linked Glycosylation, DNA Demethylation, and Ubiquitin Ligase and Hydrolase Activities to the Sin3/HDAC Complex","authors":"Pratik Goswami, Charles A.S. Banks, Janet Thornton, Bethany D. Bengs, Mihaela E. Sardiu, Laurence Florens and Michael P. Washburn*, ","doi":"10.1021/acs.jproteome.4c0049810.1021/acs.jproteome.4c00498","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00498https://doi.org/10.1021/acs.jproteome.4c00498","url":null,"abstract":"Sin3 is an evolutionarily conserved repressor protein complex mainly associated with histone deacetylase (HDAC) activity. Many proteins are part of Sin3/HDAC complexes, and the function of most of these members remains poorly understood. SAP25, a previously identified Sin3A associated protein of 25 kDa, has been proposed to participate in regulating gene expression programs involved in the immune response but the exact mechanism of this regulation is unclear. SAP25 is not expressed in HEK293 cells, which hence serve as a natural knockout system to decipher the molecular functions uniquely carried out by this Sin3/HDAC subunit. Using molecular, proteomic, protein engineering, and interaction network approaches, we show that SAP25 interacts with distinct enzymatic and regulatory protein complexes in addition to Sin3/HDAC. Additional proteins uniquely recovered from the Halo-SAP25 pull-downs included the SCF E3 ubiquitin ligase complex SKP1/FBXO3/CUL1 and the ubiquitin carboxyl-terminal hydrolase 11 (USP11). Furthermore, mutational analysis demonstrates that distinct regions of SAP25 participate in its interaction with USP11, OGT/TETs, and SCF(FBXO3). These results suggest that SAP25 may function as an adaptor protein to coordinate the assembly of different enzymatic complexes to control Sin3/HDAC-mediated gene expression. The data were deposited with the MASSIVE repository with the identifiers MSV000093576 and MSV000093553.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560438","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

Meta-Analysis and DIA-MS-Based Proteomic Investigation of COPD Patients and Asymptomatic Smokers in the Indian Population 印度人群中慢性阻塞性肺病患者和无症状吸烟者的元分析和基于 DIA-MS 的蛋白质组学研究

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-22 DOI: 10.1021/acs.jproteome.4c0046310.1021/acs.jproteome.4c00463

Gautam Sharma, Debarghya Pratim Gupta, Koustav Ganguly, Mahesh Padukudru Anand and Sanjeeva Srivastava*,

{"title":"Meta-Analysis and DIA-MS-Based Proteomic Investigation of COPD Patients and Asymptomatic Smokers in the Indian Population","authors":"Gautam Sharma, Debarghya Pratim Gupta, Koustav Ganguly, Mahesh Padukudru Anand and Sanjeeva Srivastava*, ","doi":"10.1021/acs.jproteome.4c0046310.1021/acs.jproteome.4c00463","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00463https://doi.org/10.1021/acs.jproteome.4c00463","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is India’s second largest cause of death and is largely caused by smoking. Asymptomatic smokers develop COPD due to genetic, environmental, and molecular variables, making early screening crucial. Data-independent acquisition mass spectrometry (DIA-MS) based-proteomics offers an unbiased method to analyze proteomic profiles. This study is the first to use DIA-based proteomics to analyze individual serum samples from three distinct male cohorts: healthy individuals (n = 10), asymptomatic smokers (n = 10), and COPD patients (n = 10). This comprehensive approach identified 667 proteins with a 1% false discovery rate. Differentially expressed proteins included 40 in the normal versus asymptomatic comparison, 88 in the COPD versus normal comparison, and 40 in the COPD versus asymptomatic comparison. Among them, protein-associated genes such as PRDX6, ELANE, PRKCSH, PRTN3, and MNDA could help differentiate COPD from asymptomatic smokers, while ELANE, H3-3A, IGHE, SLC4A1, and SERPINA11 could differentiate COPD from healthy subjects. Pathway enrichment and protein–protein interaction analyses revealed significant alterations in hemostasis, immune system functions, fibrin clot formation, and post-translational protein modifications. Key proteins were validated using a parallel reaction monitoring assay. DIA data are available via ProteomeXchange with identifier PXD055242. Our findings reveal key protein classifiers in COPD patients, asymptomatic smokers, and healthy individuals, helping clinicians understand disease pathobiology and improve disease management and quality of life.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560515","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

Recent Developments in Single-Cell Metabolomics by Mass Spectrometry─A Perspective. 质谱法单细胞代谢组学的最新发展--透视。

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-22 DOI: 10.1021/acs.jproteome.4c00646

Boryana Petrova, Arzu Tugce Guler

{"title":"Recent Developments in Single-Cell Metabolomics by Mass Spectrometry─A Perspective.","authors":"Boryana Petrova, Arzu Tugce Guler","doi":"10.1021/acs.jproteome.4c00646","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00646","url":null,"abstract":"Recent advancements in single-cell (sc) resolution analyses, particularly in sc transcriptomics and sc proteomics, have revolutionized our ability to probe and understand cellular heterogeneity. The study of metabolism through small molecules, metabolomics, provides an additional level of information otherwise unattainable by transcriptomics or proteomics by shedding light on the metabolic pathways that translate gene expression into functional outcomes. Metabolic heterogeneity, critical in health and disease, impacts developmental outcomes, disease progression, and treatment responses. However, dedicated approaches probing the sc metabolome have not reached the maturity of other sc omics technologies. Over the past decade, innovations in sc metabolomics have addressed some of the practical limitations, including cell isolation, signal sensitivity, and throughput. To fully exploit their potential in biological research, however, remaining challenges must be thoroughly addressed. Additionally, integrating sc metabolomics with orthogonal sc techniques will be required to validate relevant results and gain systems-level understanding. This perspective offers a broad-stroke overview of recent mass spectrometry (MS)-based sc metabolomics advancements, focusing on ongoing challenges from a biologist's viewpoint, aimed at addressing pertinent and innovative biological questions. Additionally, we emphasize the use of orthogonal approaches and showcase biological systems that these sophisticated methodologies are apt to explore.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491154","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

LineageFilter: Improved Proteotyping of Complex Samples Using Metaproteomics and Machine Learning LineageFilter：利用元蛋白质组学和机器学习改进复杂样本的蛋白质分型

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-19 DOI: 10.1021/acs.jproteome.4c0018410.1021/acs.jproteome.4c00184

Hamid Hachemi, Jean Armengaud, Lucia Grenga* and Olivier Pible,

引用次数: 0

Mannose-6-Phosphate Isomerase Functional Status Shapes a Rearrangement in the Proteome and Degradome of Mannose-Treated Melanoma Cells 甘露糖-6-磷酸异构酶的功能状态决定了甘露糖处理的黑色素瘤细胞蛋白质组和降解组的重新排列

IF 3.8 2区生物学

Journal of Proteome Research Pub Date : 2024-10-18 DOI: 10.1021/acs.jproteome.4c0070510.1021/acs.jproteome.4c00705

Nathália de Vasconcellos Racorti, Matheus Martinelli, Silvina Odete Bustos, Murilo Salardani, Maurício Frota Camacho, Uilla Barcick, Luis Roberto Fonseca Lima, Letícia Dias Lima Jedlicka, Claudia Barbosa Ladeira de Campos, Richard Hemmi Valente, Roger Chammas and André Zelanis*,

{"title":"Mannose-6-Phosphate Isomerase Functional Status Shapes a Rearrangement in the Proteome and Degradome of Mannose-Treated Melanoma Cells","authors":"Nathália de Vasconcellos Racorti, Matheus Martinelli, Silvina Odete Bustos, Murilo Salardani, Maurício Frota Camacho, Uilla Barcick, Luis Roberto Fonseca Lima, Letícia Dias Lima Jedlicka, Claudia Barbosa Ladeira de Campos, Richard Hemmi Valente, Roger Chammas and André Zelanis*, ","doi":"10.1021/acs.jproteome.4c0070510.1021/acs.jproteome.4c00705","DOIUrl":"https://doi.org/10.1021/acs.jproteome.4c00705https://doi.org/10.1021/acs.jproteome.4c00705","url":null,"abstract":"Metabolic reprogramming is a ubiquitous feature of transformed cells, comprising one of the hallmarks of cancer and enabling neoplastic cells to adapt to new environments. Accumulated evidence reports on the failure of some neoplastic cells to convert mannose-6-phosphate into fructose-6-phosphate, thereby impairing tumor growth in cells displaying low levels of mannose-6-phosphate isomerase (MPI). Thus, we performed functional analyses and profiled the proteome landscape and the repertoire of substrates of proteases (degradome) of melanoma cell lines with distinct mutational backgrounds submitted to treatment with mannose. Our results suggest a significant rearrangement in the proteome and degradome of melanoma cell lines upon mannose treatment including the activation of catabolic pathways (such as protein turnover) and differences in protein N-terminal acetylation. Even though MPI protein abundance and gene expression status are not prognostic markers, perturbation in the network caused by an exogenous monosaccharide source (i.e., mannose) significantly affected the downstream interconnected biological circuitry. Therefore, as reported in this study, the proteomic/degradomic mapping of mannose downstream effects due to the metabolic rewiring caused by the functional status of the MPI enzyme could lead to the identification of specific molecular players from affected signaling circuits in melanoma.","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.jproteome.4c00705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560504","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