{"title":"基于 LC-Orbitrap HRMS 的蛋白质组学揭示了与果蝇 RasV12 诱导的胶质母细胞瘤 (GBM) 相关的新型线粒体动力学调控蛋白。","authors":"Pradeep Kumar, Rohit Kumar, Prabhat Kumar, Sunaina Kushwaha, Sandhya Kumari, Neha Yadav, Saripella Srikrishna","doi":"10.1021/acs.jproteome.4c00502","DOIUrl":null,"url":null,"abstract":"<p><p>Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor found in adult humans with a poor prognosis and average survival of 14-15 months. In order to have a comprehensive understanding of proteome and identify novel therapeutic targets, this study focused mainly on the differentially abundant proteins (DAPs) of <i>Ras</i><sup><i>V12</i></sup>-induced GBM. <i>Ras</i><sup><i>V12</i></sup> is a constitutively active Ras mutant form essential for tumor progression by continuously activating signaling pathways leading to uncontrolled tumor growth. This study used a transgenic <i>Drosophila</i> model with <i>Ras</i><sup><i>V12</i></sup> overexpression using the <i>repo-GAL4</i> driver line, specifically in glial cells, to study GBM. The high-resolution mass spectrometry (HRMS)-based proteomic analysis of the GBM larval central nervous system identified three novel DAPs specific to mitochondria. These DAPs, probable maleylacetoacetate isomerase 2 (Q9VHD2), bifunctional methylene tetrahydrofolate dehydrogenase (Q04448), and glutamine synthetase1 (P20477), identified through HRMS were further validated by qRT-PCR. The protein-protein interaction analysis revealed interactions between Ras<sup>V12</sup> and DAPs, with functional links to mitochondrial dynamics regulators such as Drp1, Marf, Parkin, and HtrA2. Notably, altered expressions of Q9VHD2, P20477, and Q04448 were observed during GBM progression, which offers new insights into the involvement of mitochondrial dynamic regulators in <i>Ras</i><sup><i>V12</i></sup>-induced GBM pathophysiology.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":"5030-5047"},"PeriodicalIF":3.8000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"LC-Orbitrap HRMS-Based Proteomics Reveals Novel Mitochondrial Dynamics Regulatory Proteins Associated with <i>Ras</i><i>V12-</i>Induced Glioblastoma (GBM) of <i>Drosophila</i>.\",\"authors\":\"Pradeep Kumar, Rohit Kumar, Prabhat Kumar, Sunaina Kushwaha, Sandhya Kumari, Neha Yadav, Saripella Srikrishna\",\"doi\":\"10.1021/acs.jproteome.4c00502\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor found in adult humans with a poor prognosis and average survival of 14-15 months. In order to have a comprehensive understanding of proteome and identify novel therapeutic targets, this study focused mainly on the differentially abundant proteins (DAPs) of <i>Ras</i><sup><i>V12</i></sup>-induced GBM. <i>Ras</i><sup><i>V12</i></sup> is a constitutively active Ras mutant form essential for tumor progression by continuously activating signaling pathways leading to uncontrolled tumor growth. This study used a transgenic <i>Drosophila</i> model with <i>Ras</i><sup><i>V12</i></sup> overexpression using the <i>repo-GAL4</i> driver line, specifically in glial cells, to study GBM. The high-resolution mass spectrometry (HRMS)-based proteomic analysis of the GBM larval central nervous system identified three novel DAPs specific to mitochondria. These DAPs, probable maleylacetoacetate isomerase 2 (Q9VHD2), bifunctional methylene tetrahydrofolate dehydrogenase (Q04448), and glutamine synthetase1 (P20477), identified through HRMS were further validated by qRT-PCR. The protein-protein interaction analysis revealed interactions between Ras<sup>V12</sup> and DAPs, with functional links to mitochondrial dynamics regulators such as Drp1, Marf, Parkin, and HtrA2. Notably, altered expressions of Q9VHD2, P20477, and Q04448 were observed during GBM progression, which offers new insights into the involvement of mitochondrial dynamic regulators in <i>Ras</i><sup><i>V12</i></sup>-induced GBM pathophysiology.</p>\",\"PeriodicalId\":48,\"journal\":{\"name\":\"Journal of Proteome Research\",\"volume\":\" \",\"pages\":\"5030-5047\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Proteome Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.jproteome.4c00502\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Proteome Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jproteome.4c00502","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/16 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
LC-Orbitrap HRMS-Based Proteomics Reveals Novel Mitochondrial Dynamics Regulatory Proteins Associated with RasV12-Induced Glioblastoma (GBM) of Drosophila.
Glioblastoma multiforme (GBM) is the most prevalent and aggressive brain tumor found in adult humans with a poor prognosis and average survival of 14-15 months. In order to have a comprehensive understanding of proteome and identify novel therapeutic targets, this study focused mainly on the differentially abundant proteins (DAPs) of RasV12-induced GBM. RasV12 is a constitutively active Ras mutant form essential for tumor progression by continuously activating signaling pathways leading to uncontrolled tumor growth. This study used a transgenic Drosophila model with RasV12 overexpression using the repo-GAL4 driver line, specifically in glial cells, to study GBM. The high-resolution mass spectrometry (HRMS)-based proteomic analysis of the GBM larval central nervous system identified three novel DAPs specific to mitochondria. These DAPs, probable maleylacetoacetate isomerase 2 (Q9VHD2), bifunctional methylene tetrahydrofolate dehydrogenase (Q04448), and glutamine synthetase1 (P20477), identified through HRMS were further validated by qRT-PCR. The protein-protein interaction analysis revealed interactions between RasV12 and DAPs, with functional links to mitochondrial dynamics regulators such as Drp1, Marf, Parkin, and HtrA2. Notably, altered expressions of Q9VHD2, P20477, and Q04448 were observed during GBM progression, which offers new insights into the involvement of mitochondrial dynamic regulators in RasV12-induced GBM pathophysiology.
期刊介绍:
Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".