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Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites.

ABSTRACT: Proteins of all living cells undergo a myriad of post-translational modifications (PTMs) that are critical to multifarious life processes. In this study, we describe the first comprehensive multiple PTM-omics atlas in parallel with quantitative proteome analyses of two representative species of African trypanosomes, Trypanosoma brucei and Trypanosoma evansi. Ten PTM types with approximately 40,000 modified sites and 150 histone marks with a fine map on each protein of the two African trypanosomes were accomplished. The two biologically different trypanosomal species displayed distinct PTM-omic features, regulation pathways, and networks. Modifications in the proteins involved in the redox system were mainly upregulated in T. brucei, whereas proteins associated with motility were predominantly modified in T. evansi. The establishment of a database of multiple PTMs in the two parasites provides us with a deep insight into the biological mechanisms that underpin life processes in trypanosomes with different life cycles.

SUBMITTER: Zhang N

PROVIDER: S-EPMC7218301 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites.

Zhang Naiwen N Jiang Ning N Zhang Kai K Zheng Lili L Zhang Di D Sang Xiaoyu X Feng Ying Y Chen Ran R Yang Na N Wang Xinyi X Cheng Zhongyi Z Suo Xun X Lun Zhaorong Z Chen Qijun Q

iScience 20200418 5

Proteins of all living cells undergo a myriad of post-translational modifications (PTMs) that are critical to multifarious life processes. In this study, we describe the first comprehensive multiple PTM-omics atlas in parallel with quantitative proteome analyses of two representative species of African trypanosomes, Trypanosoma brucei and Trypanosoma evansi. Ten PTM types with approximately 40,000 modified sites and 150 histone marks with a fine map on each protein of the two African trypanosome ...[more]

PMID: 32403088

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Project description:BackgroundGliomas represent the most aggressive malignancies of the central nervous system, with posttranslational modifications (PTMs) emerging as critical regulators of oncogenic processes through dynamic protein functional modulation. Despite their established role in tumor biology, the systematic characterization of PTM-mediated molecular mechanisms driving glioma progression remains unexplored. This study aims to uncover the molecular mechanisms of glioma, with a focus on the role of PTMs.MethodsWe analyzed the PTM pathway to classify glioma patients into distinct clusters. Comprehensive analyses compared intercluster differences in clinical outcomes, mutational landscapes, and immune microenvironment profiles. Differentially expressed genes (DEGs) were identified to construct a robust prognostic prediction model with machine learning approaches. Among the genes included in the model, TOM1L1 (Target of Myb1 Like 1 Membrane Trafficking Protein) was selected for in vitro experimental validation to assess its role in glioma progression.ResultsPTMs were found to influence glioma prognosis significantly. Dysregulation in specific pathways, such as glutathionylation and citrullination, was correlated with more aggressive clinical features. The prognostic model, comprising DEGs such as TOM1L1, demonstrated high predictive accuracy (c-index = 0.867)-the scores derived from the model strongly correlated with glioma progression indicators. In vitro experiments revealed that TOM1L1 facilitates malignant progression by modulating PTM pathways, confirming its functional role in glioma.ConclusionOur study establishes the first comprehensive PTM atlas in gliomas, revealing subtype-specific modification patterns with clinical and therapeutic implications. TOM1L1 emerges as a promising prognostic biomarker and a potential therapeutic intervention target. Targeting PTM pathways may offer novel strategies for glioma treatment, enhancing patient outcomes.

Dataset Information

Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites.

Publications

Landscapes of Protein Posttranslational Modifications of African Trypanosoma Parasites.

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