Molecular & Cellular Proteomics最新文献

Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-treated Pancreatic Beta Cells. 综合多PTM蛋白质组学揭示了细胞因子处理的胰腺β细胞中动态的全局、氧化还原、磷酸化和乙酰化调控。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-14 DOI: 10.1016/j.mcpro.2024.100881

Austin Gluth, Xiaolu Li, Marina A Gritsenko, Matthew J Gaffrey, Doo Nam Kim, Priscila M Lalli, Rosalie K Chu, Nicholas J Day, Tyler J Sagendorf, Matthew E Monroe, Song Feng, Tao Liu, Bin Yang, Wei-Jun Qian, Tong Zhang

{"title":"Integrative Multi-PTM Proteomics Reveals Dynamic Global, Redox, Phosphorylation, and Acetylation Regulation in Cytokine-treated Pancreatic Beta Cells.","authors":"Austin Gluth, Xiaolu Li, Marina A Gritsenko, Matthew J Gaffrey, Doo Nam Kim, Priscila M Lalli, Rosalie K Chu, Nicholas J Day, Tyler J Sagendorf, Matthew E Monroe, Song Feng, Tao Liu, Bin Yang, Wei-Jun Qian, Tong Zhang","doi":"10.1016/j.mcpro.2024.100881","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100881","url":null,"abstract":"Studying regulation of protein function at a systems level necessitates an understanding of the interplay among diverse post-translational modifications (PTMs). A variety of proteomics sample processing workflows are currently used to study specific PTMs but rarely characterize multiple types of PTMs from the same sample inputs. Method incompatibilities and laborious sample preparation steps complicate large-scale physiological investigations and can lead to variations in results. The single-pot, solid-phase-enhanced sample preparation (SP3) method for sample cleanup is compatible with different lysis buffers and amenable to automation, making it attractive for high-throughput multi-PTM profiling. Herein, we describe an integrative SP3 workflow for multiplexed quantification of protein abundance, cysteine thiol oxidation, phosphorylation, and acetylation. The broad applicability of this approach is demonstrated using cell and tissue samples, and its utility for studying interacting regulatory networks is highlighted in a time-course experiment of cytokine-treated β-cells. We observed a swift response in global regulation of protein abundances consistent with rapid activation of JAK-STAT and NF-κB signaling pathways. Regulators of these pathways as well as proteins involved in their target processes displayed multi-PTM dynamics indicative of a complex cellular response stages: acute, adaptation, and chronic (prolonged stress). PARP14, a negative regulator of JAK-STAT, had multiple co-localized PTMs that may be involved in intraprotein regulatory crosstalk. Our workflow provides a high-throughput platform that can profile multi-PTMomes from the same sample set, which is valuable in unraveling the functional roles of PTMs and their co-regulation.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100881"},"PeriodicalIF":6.1,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644266","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

Gradient-Elution Nanoflow Liquid Chromatography without a Binary Pump: Smoothed Step Gradients Enable Reproducible, Sensitive, and Low-Cost Separations for Single-Cell Proteomics. 无需二进制泵的梯度洗脱纳升液相色谱法：平滑阶梯梯度使单细胞蛋白质组学的分离具有可重复性、灵敏性和低成本性

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-11 DOI: 10.1016/j.mcpro.2024.100880

Kei G I Webber, Siqi Huang, Hsien-Jung L Lin, Tyler L Hunter, Jeremy Tsang, Dasun Jayatunge, Joshua L Andersen, Ryan T Kelly

{"title":"Gradient-Elution Nanoflow Liquid Chromatography without a Binary Pump: Smoothed Step Gradients Enable Reproducible, Sensitive, and Low-Cost Separations for Single-Cell Proteomics.","authors":"Kei G I Webber, Siqi Huang, Hsien-Jung L Lin, Tyler L Hunter, Jeremy Tsang, Dasun Jayatunge, Joshua L Andersen, Ryan T Kelly","doi":"10.1016/j.mcpro.2024.100880","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100880","url":null,"abstract":"Mass spectrometry-based proteome profiling of trace analytes including single cells benefits from liquid chromatography separations operated at low flow rates (e.g., <50 nL/min). However, high-pressure binary pumps needed to achieve such flow rates are not commercially available, and instead require splitting of the gradient flow to achieve low-nanoliter-per-minute flow rates. Gradient flow splitting can waste solvent and lead to flow inconsistencies. To address this, we have developed a method for creating gradients by combining plugs of mobile phase of increasing solvent strength together in a column, and then relying on Taylor dispersion to form the desired smooth gradient profile. Additionally, our method dramatically reduces costs, as only a single isocratic high-pressure pump is required. Following development of gradient profiles for both 10- and 20-min active gradients, we measured 200 pg injections of HeLa digest using a timsTOF mass spectrometer. Finally, we investigated differences in protein expression between single cells originating from two different colonies of ATG-knockout HeLa cells. Thousands of proteins were quantified, and a potential mechanism explaining differential immune responses of these two colonies upon exposure to viral DNA treatment was determined.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100880"},"PeriodicalIF":6.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624001","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 analysis of miRNA binding sites reveals the complex response of uterine epithelium to miR-26a-5p and miR-125b-5p during early pregnancy. 对 miRNA 结合位点的深入分析揭示了妊娠早期子宫上皮对 miR-26a-5p 和 miR-125b-5p 的复杂反应。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-11 DOI: 10.1016/j.mcpro.2024.100879

Kamil Myszczynski, Joanna Szuszkiewicz, Kamil Krawczynski, Małgorzata Sikora, Marta Romaniewicz, Maria M Guzewska, Piotr Zabielski, Monika M Kaczmarek

{"title":"In-depth analysis of miRNA binding sites reveals the complex response of uterine epithelium to miR-26a-5p and miR-125b-5p during early pregnancy.","authors":"Kamil Myszczynski, Joanna Szuszkiewicz, Kamil Krawczynski, Małgorzata Sikora, Marta Romaniewicz, Maria M Guzewska, Piotr Zabielski, Monika M Kaczmarek","doi":"10.1016/j.mcpro.2024.100879","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100879","url":null,"abstract":"Post-transcriptional regulation of gene expression by miRNAs likely makes significant contributions to mRNA abundance at the embryo-maternal interface. In this study, we investigated how miR-26a-5p and miR-125b-5p contribute to molecular changes occurring in the uterine luminal epithelium, which serves as the first site of signal exchange between the mother and developing embryo. To measure de novo protein synthesis after miRNA delivery to primary uterine luminal epithelial cells, we employed pulsed stable isotope labeling by amino acids (pSILAC). We found that both miRNAs alter the proteome of luminal epithelial cells, impacting numerous cellular functions, immune responses, as well as intracellular and second messenger signaling pathways. Additionally, we identified several features of miRNA-mRNA interactions that may influence the targeting efficiency of miR-26a-5p and miR-125b-5p. Overall, our study suggests a complex interaction of miR-26a-5p and miR-125b-5p with their respective targets. However, both appear to cooperatively function in modulating the cellular environment of the luminal epithelium, facilitating the morphological and molecular changes that occur during the intensive communication between the embryo and uterus at pregnancy.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100879"},"PeriodicalIF":6.1,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624004","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

Knockdown proteomics reveals USP7 as a regulator of cell-cell adhesion in colorectal cancer via AJUBA. 基因敲除蛋白质组学揭示 USP7 是通过 AJUBA 调节结直肠癌细胞-细胞粘附的调控因子。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-08 DOI: 10.1016/j.mcpro.2024.100878

Ahood Al-Eidan, Ben Draper, Siyuan Wang, Brandon Coke, Paul Skipp, Yihua Wang, Rob M Ewing

{"title":"Knockdown proteomics reveals USP7 as a regulator of cell-cell adhesion in colorectal cancer via AJUBA.","authors":"Ahood Al-Eidan, Ben Draper, Siyuan Wang, Brandon Coke, Paul Skipp, Yihua Wang, Rob M Ewing","doi":"10.1016/j.mcpro.2024.100878","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100878","url":null,"abstract":"Ubiquitin-specific protease 7 (USP7) is implicated in many cancers including colorectal cancer in which it regulates cellular pathways such as Wnt signalling and the P53-MDM2 pathway. With the discovery of small-molecule inhibitors, USP7 has also become a promising target for cancer therapy, and therefore systematically identifying USP7 deubiquitinase interaction partners and substrates has become an important goal. In this study, we selected a colorectal cancer cell model that is highly dependent on USP7 and in which USP7 knockdown significantly inhibited colorectal cancer cell viability, colony formation, and cell-cell adhesion. We then used inducible knockdown of USP7 followed by LC-MS/MS to quantify USP7 dependent proteins. We identified the Ajuba LIM domain protein as an interacting partner of USP7 through co-IP, its substantially reduced protein levels in response to USP7 knockdown, and its sensitivity to the specific USP7 inhibitor FT671. The Ajuba protein has been shown to have oncogenic functions in colorectal and other tumours, including regulation of cell-cell adhesion. We show that both knockdown of USP7 or Ajuba results in a substantial reduction of cell-cell adhesion, with concomitant effects on other proteins associated with adherens junctions. Our findings underlie the role of USP7 in colorectal cancer through its protein interaction networks and show that the Ajuba protein is a component of USP7 protein networks present in colorectal cancer.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100878"},"PeriodicalIF":6.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624008","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

Bridging the Gap from Proteomics Technology to Clinical Application: Highlights from the 68^th Benzon Foundation Symposium. 缩小蛋白质组学技术与临床应用之间的差距：第 68 届 Benzon 基金会研讨会花絮。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-08 DOI: 10.1016/j.mcpro.2024.100877

Vincent Albrecht, Johannes Müller-Reif, Thierry M Nordmann, Andreas Mund, Lisa Schweizer, Philipp E Geyer, Lili Niu, Juanjuan Wang, Frederik Post, Marc Oeller, Andreas Metousis, Annelaura Bach Nielsen, Medini Steger, Nicolai J Wewer Albrechtsen, Matthias Mann

{"title":"Bridging the Gap from Proteomics Technology to Clinical Application: Highlights from the 68th Benzon Foundation Symposium.","authors":"Vincent Albrecht, Johannes Müller-Reif, Thierry M Nordmann, Andreas Mund, Lisa Schweizer, Philipp E Geyer, Lili Niu, Juanjuan Wang, Frederik Post, Marc Oeller, Andreas Metousis, Annelaura Bach Nielsen, Medini Steger, Nicolai J Wewer Albrechtsen, Matthias Mann","doi":"10.1016/j.mcpro.2024.100877","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100877","url":null,"abstract":"The 68th Benzon Foundation Symposium brought together leading experts to explore the integration of mass spectrometry (MS)-based proteomics and artificial intelligence in revolutionizing personalized medicine. This report highlights key discussions on recent technological advances in MS-based proteomics, including improvements in sensitivity, throughput, and data analysis. Particular emphasis was placed on plasma proteomics and its potential for biomarker discovery across various diseases. The symposium addressed critical challenges in translating proteomic discoveries to clinical practice, including standardization, regulatory considerations and the need for robust 'business cases' to motivate adoption. Promising applications were presented in areas such as cancer diagnostics, neurodegenerative diseases, and cardiovascular health. The integration of proteomics with other omics technologies and imaging methods was explored, showcasing the power of multi-modal approaches in understanding complex biological systems. Artificial intelligence emerged as a crucial tool for the acquisition of large-scale proteomic datasets, extracting meaningful insights, and enhancing clinical decision-making. By fostering dialogue between academic researchers, industry leaders in proteomics technology, and clinicians, the symposium illuminated potential pathways for proteomics to transform personalized medicine, advancing the cause of more precise diagnostics and targeted therapies.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100877"},"PeriodicalIF":6.1,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623998","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

Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression. 自上而下的蛋白质组学识别肝硬化进展的血浆蛋白质形式特征

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-07 DOI: 10.1016/j.mcpro.2024.100876

Eleonora Forte, Jes M Sanders, Indira Pla, Vijaya Lakshmi Kanchustambham, Michael A R Hollas, Che-Fan Huang, Aniel Sanchez, Katrina N Peterson, Rafael D Melani, Alexander Huang, Praneet Polineni, Julianna M Doll, Zachary Dietch, Neil L Kelleher, Daniela P Ladner

{"title":"Top-Down Proteomics Identifies Plasma Proteoform Signatures of Liver Cirrhosis Progression.","authors":"Eleonora Forte, Jes M Sanders, Indira Pla, Vijaya Lakshmi Kanchustambham, Michael A R Hollas, Che-Fan Huang, Aniel Sanchez, Katrina N Peterson, Rafael D Melani, Alexander Huang, Praneet Polineni, Julianna M Doll, Zachary Dietch, Neil L Kelleher, Daniela P Ladner","doi":"10.1016/j.mcpro.2024.100876","DOIUrl":"10.1016/j.mcpro.2024.100876","url":null,"abstract":"Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care and reduce morbidity and mortality. Therefore, it is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to identify differentially expressed proteoforms (DEPs) in the plasma of patients with progressive stages of liver cirrhosis with the ultimate goal to identify candidate biomarkers of disease progression. In this pilot study, we identified 209 DEPs across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the three stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in several metabolic and immunological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100876"},"PeriodicalIF":6.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624016","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

The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry. Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-06 DOI: 10.1016/j.mcpro.2024.100875

Lissa C Anderson, Dina L Bai, Greg T Blakney, David S Butcher, Larry Reser, Jeffrey Shabanowitz

{"title":"The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry.","authors":"Lissa C Anderson, Dina L Bai, Greg T Blakney, David S Butcher, Larry Reser, Jeffrey Shabanowitz","doi":"10.1016/j.mcpro.2024.100875","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100875","url":null,"abstract":"Donald Hunt has made seminal contributions to the fields of proteomics, immunology, epigenetics, and glycobiology. The foundation of every important work to come out of the Hunt Laboratory is de novo peptide sequencing. For decades, he taught hundreds of students, postdocs, engineers, and scientists to directly interpret mass spectral data. To honor his legacy and ensure that the art of de novo sequencing is not lost, we have adapted his teaching materials into \"The Hunt Lab Guide to De Novo Peptide Sequence Analysis by Tandem Mass Spectrometry\". In addition to the de novo sequencing tutorials, we present two freely available software tools that facilitate manual interpretation of mass spectra and validation of search results. The first, \"Hunt Lab Peptide Fragment Calculator\", calculates precursor and fragment mass-to-charge ratios for any peptide. The second program, \"Predator Protein Fragment Calculator\", was inspired in part by the fragment calculator developed in the Hunt Lab. Its capabilities are enhanced to facilitate interpretation of mass spectral data derived from intact proteins. We hope that the combination of these educational tools will continue to benefit students and researchers by empowering them to interpret data on their own.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100875"},"PeriodicalIF":6.1,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624012","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

Early Days in the Hunt Laboratory at UVA, 1969-1980. 弗吉尼亚大学亨特实验室的早期生活，1969-1980 年。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-04 DOI: 10.1016/j.mcpro.2024.100874

P Jane Gale, George C Stafford, Howard R Morris, Charles N McEwen

{"title":"Early Days in the Hunt Laboratory at UVA, 1969-1980.","authors":"P Jane Gale, George C Stafford, Howard R Morris, Charles N McEwen","doi":"10.1016/j.mcpro.2024.100874","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100874","url":null,"abstract":"Arriving at the University of Virginia in the autumn of 1969, Donald Hunt began his 50+ year career in academics with the study of organometallic chemistry, on which he had done his PhD thesis, and mass spectrometry, to which he was introduced while a postdoc in Klaus Biemann's laboratory at the Massachusetts Institute of Technology. In the 1970s, Hunt's lab pioneered the use of negative chemical ionization (CI) to enhance sensitivity for studying organic molecules, developed a system for simultaneously obtaining positive and negative CI spectra to augment structure elucidation, and built a prototype triple quadrupole instrument so effective at collisional dissociation that its commercial counterpart became the analytical instrument of choice for mixture analysis for the next decade and beyond. Foreseeing that the future lay in the analysis of biological molecules, by the end of the decade Hunt shifted his focus to peptides. The analysis of protein fragments had suddenly become more accessible thanks to the advent of the triple quadrupole and Barber's invention of fast atom bombardment. As the '80s began and Hunt and his team sought to pursue larger and larger pieces of proteins, his attention turned to the development of mass spectrometers with greater mass range. While recounting their memories of these events, several of Hunt's students and colleagues pay tribute to his support for them as individuals, as well as to his infectious enthusiasm for scientific endeavors that he so generously shared.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100874"},"PeriodicalIF":6.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591248","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

On the Hunt for the Histone Code. 寻找组蛋白密码

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-01 DOI: 10.1016/j.mcpro.2024.100873

Beatrix M Ueberheide, Sahana Mollah, Benjamin A Garcia

{"title":"On the Hunt for the Histone Code.","authors":"Beatrix M Ueberheide, Sahana Mollah, Benjamin A Garcia","doi":"10.1016/j.mcpro.2024.100873","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100873","url":null,"abstract":"Our genome is not made of naked DNA, but a fiber (chromatin) composed of DNA and proteins packaged into our chromosomes. The basic building block of chromatin is the nucleosome, which has two copies of each of the proteins called histones (H2A, H2B, H3, and H4) wrapped by 146 base pairs of DNA. Regions of our genetic material are found between the more open (euchromatin) and more compact (heterochromatin) regions of the genome that can be variably accessible to the underlying genes. Furthermore, post-translational modifications (PTMs) on histones, such as on H3, are critical for regulating chromatin accessibility and gene expression. While site specific antibodies were the tool of choice for histone PTM analysis in the early days (pre-2000s), enter Don Hunt changing the histone PTM field forever. Don's clever thinking brought new innovative mass spectrometry-based approaches to the epigenetics field. His lab's effort led to the discovery of many new histone modifications and methods to facilitate the detection and quantification of histone PTMs, which are still considered state of the art in the proteomics field today. Due to Don's pioneering work in this area, many labs have been able to jump into the epigenetics field and \"Hunt\" down their own histone targets. A walkthrough of those early histone years in the Hunt Lab are described by three of us who were fortunate enough to be at the right place, at the right time.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100873"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568025","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

Screening of cancer-specific biomarkers for hepatitis B-related hepatocellular carcinoma based on a proteome microarray. 基于蛋白质组芯片筛选乙型肝炎相关肝细胞癌的癌症特异性生物标记物。

IF 6.1 2区生物学

Molecular & Cellular Proteomics Pub Date : 2024-11-01 DOI: 10.1016/j.mcpro.2024.100872

Wudi Hao, Danyang Zhao, Yuan Meng, Mei Yang, Meichen Ma, Jingwen Hu, Jianhua Liu, Xiaosong Qin

{"title":"Screening of cancer-specific biomarkers for hepatitis B-related hepatocellular carcinoma based on a proteome microarray.","authors":"Wudi Hao, Danyang Zhao, Yuan Meng, Mei Yang, Meichen Ma, Jingwen Hu, Jianhua Liu, Xiaosong Qin","doi":"10.1016/j.mcpro.2024.100872","DOIUrl":"https://doi.org/10.1016/j.mcpro.2024.100872","url":null,"abstract":"Hepatocellular carcinoma (HCC) is associated with one of the highest mortality rates among cancers, rendering its early diagnosis clinically invaluable. Serum biomarkers, specifically alpha-fetoprotein (AFP), represent the most promising and widely used diagnostic biomarkers for HCC. However, its detection rate is low in the early stages of HCC progression, and distinguishing specific false positives for other liver-related diseases, such as cirrhosis and acute hepatitis, remains challenging. Therefore, this study was conducted to identify biomarkers for hepatitis B (HBV)-related liver diseases by screening differentially expressed autoantibodies against tumor-associated antigens (TAAbs). We designed a large-scale multistage investigation, encompassing initial screening, HCC-focused, and ELISA validation cohorts to identify potential TAAbs in HBV-related liver diseases, spanning from healthy control (HC) individuals to patients with chronic hepatitis B (CHB), hepatitis B-related cirrhosis (HBC), and HCC, using protein microarray technology. The differential biological characteristics of TAAbs were analyzed using bioinformatics analysis. Validation of tumor-specific biomarkers for HCC was performed using ELISA. In the screening cohort, 547 candidate TAAbs were identified in the HCC group compared to those in the HC group. In the HCC-focused cohort, 64, 61, and 65 candidate TAAbs were identified in the CHB, HBC, and HCC groups, respectively, compared to those in the HC group. Thirty-four proteins exhibited continuously elevated expression from HCs to patients with CHB, HBC, and HCC. Among these, nine were identified as cancer-specific proteins. In the validation cohort, UBE2Z, CNOT3, and EID3 were correlated with liver function indicators in patients with hepatitis B-related HCC. Overall, UBE2Z, CNOT3, and EID3 emerged as cancer-specific biomarkers for HBV-related liver disease, providing a scientific basis for clinical application.","PeriodicalId":18712,"journal":{"name":"Molecular & Cellular Proteomics","volume":" ","pages":"100872"},"PeriodicalIF":6.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568004","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