Protein posttranslational modification (PTM) by glycation: Role in lens aging and age-related cataractogenesis

O-glycosylation is a protein posttranslational modification important in regulating almost all cells. It is related to a large number of physiological and pathological phenomena. Recognizing O-glycosylation sites is the key to further investigating the molecular mechanism of protein posttranslational modification. This study aimed to collect a reliable dataset on Homo sapiens and develop an O-glycosylation predictor for Homo sapiens, named Captor, through multiple features. A random undersampling method and a synthetic minority oversampling technique were employed to deal with imbalanced data. In addition, the Kruskal–Wallis (K–W) test was adopted to optimize feature vectors and improve the performance of the model. A support vector machine, due to its optimal performance, was used to train and optimize the final prediction model after a comprehensive comparison of various classifiers in traditional machine learning methods and deep learning. On the independent test set, Captor outperformed the existing O-glycosylation tool, suggesting that Captor could provide more instructive guidance for further experimental research on O-glycosylation. The source code and datasets are available at https://github.com/YanZhu06/Captor/ .

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Protein Posttranslational Modification: A Potential Target in Pharmaceutical Development

Pharmaceutical Sciences Encyclopedia ◽

10.1002/9780470571224.pse302 ◽

2010 ◽

Cited By ~ 2

Author(s):

M.D. Mostaqul Huq ◽

Li-Na Wei

Keyword(s):

Posttranslational Modification ◽

Pharmaceutical Development ◽

Potential Target ◽

Protein Posttranslational Modification

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Age-related loss of neural stem cell O-GlcNAc promotes a glial fate switch through STAT3 activation

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2007439117 ◽

2020 ◽

Vol 117 (36) ◽

pp. 22214-22224 ◽

Cited By ~ 1

Author(s):

Charles W. White ◽

Xuelai Fan ◽

Jason C. Maynard ◽

Elizabeth G. Wheatley ◽

Gregor Bieri ◽

...

Keyword(s):

Stem Cell ◽

Neural Stem Cell ◽

Posttranslational Modification ◽

Site Directed Mutagenesis ◽

Mass Spectrometry Analysis ◽

Spectrometry Analysis ◽

Age Related ◽

Astrocyte Differentiation ◽

Glial Fate

Increased neural stem cell (NSC) quiescence is a major determinant of age-related regenerative decline in the adult hippocampus. However, a coextensive model has been proposed in which division-coupled conversion of NSCs into differentiated astrocytes restrict the stem cell pool with age. Here we report that age-related loss of the posttranslational modification, O-linked β-N-acetylglucosamine (O-GlcNAc), in NSCs promotes a glial fate switch. We detect an age-dependent decrease in NSC O-GlcNAc levels coincident with decreased neurogenesis and increased gliogenesis in the mature hippocampus. Mimicking an age-related loss of NSC O-GlcNAcylation in young mice reduces neurogenesis, increases astrocyte differentiation, and impairs associated cognitive function. Using RNA-sequencing of primary NSCs following decreased O-GlcNAcylation, we detected changes in the STAT3 signaling pathway indicative of glial differentiation. Moreover, using O-GlcNAc–specific mass spectrometry analysis of the aging hippocampus, together with an in vitro site-directed mutagenesis approach, we identify loss of STAT3 O-GlcNAc at Threonine 717 as a driver of astrocyte differentiation. Our data identify the posttranslational modification, O-GlcNAc, as a key molecular regulator of regenerative decline underlying an age-related NSC fate switch.

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Evaluation of Nonenzymatic Posttranslational Modification–Derived Products as Biomarkers of Molecular Aging of Proteins

Clinical Chemistry ◽

10.1373/clinchem.2010.145201 ◽

2010 ◽

Vol 56 (9) ◽

pp. 1401-1412 ◽

Cited By ~ 81

Author(s):

Stéphane Jaisson ◽

Philippe Gillery

Keyword(s):

Posttranslational Modifications ◽

Posttranslational Modification ◽

New Technologies ◽

Clinical Chemistry ◽

Routine Practice ◽

Potential Contribution ◽

Age Related ◽

Specificity And Sensitivity ◽

Molecular Aging

BACKGROUND During their biological life, proteins are exposed in a cumulative fashion to irreversible nonenzymatic, late posttranslational modifications that are responsible for their molecular aging. It is now well established that these damaged proteins constitute a molecular substratum for many dysfunctions described in metabolic and age-related diseases, such as diabetes mellitus, renal insufficiency, atherosclerosis, or neurodegenerative diseases. Accordingly, the specific end products derived from these reactions are considered potentially useful biomarkers for these diseases. CONTENT The aim of this review is to give an overview of nonenzymatic posttranslational modifications of proteins and their influence in vivo, take inventory of the analytical methods available for the measurement of posttranslational modification–derived products, and assess the potential contribution of new technologies for their clinical use as biological markers of protein molecular aging. SUMMARY Despite their clinical relevance, biomarkers of posttranslational modifications of proteins have been studied only in the context of experimental clinical research, owing to the analytical complexity of their measurement. The recent implementation in clinical chemistry laboratories of mass spectrometry–based methods that provide higher specificity and sensitivity has facilitated the measurement of these compounds. These markers are not used currently by clinicians in routine practice, however, and many challenges, such as standardization, have to be confronted before these markers can be used as efficient tools in the detection and monitoring of long-term complications of metabolic and age-related diseases.

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Protein Posttranslational Modification: A Potential Target in Pharmaceutical Development

Handbook of Pharmaceutical Biotechnology ◽

10.1002/9780470117118.ch4d ◽

2007 ◽

pp. 417-441 ◽

Cited By ~ 1

Author(s):

M.D. Mostaqul Huq ◽

Li-Na Wei

Keyword(s):

Posttranslational Modification ◽

Pharmaceutical Development ◽

Potential Target ◽

Protein Posttranslational Modification

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Lysine Glutarylation Is a Protein Posttranslational Modification Regulated by SIRT5

Cell Metabolism ◽

10.1016/j.cmet.2014.03.014 ◽

2014 ◽

Vol 19 (4) ◽

pp. 605-617 ◽

Cited By ~ 380

Author(s):

Minjia Tan ◽

Chao Peng ◽

Kristin A. Anderson ◽

Peter Chhoy ◽

Zhongyu Xie ◽

...

Keyword(s):

Posttranslational Modification ◽

Protein Posttranslational Modification

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Quantitative proteomics analysis of lysine 2-hydroxyisobutyrylation in IgA nephropathy

Clinical Proteomics ◽

10.1186/s12014-021-09314-0 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Shaoying Huang ◽

Fengping Zheng ◽

Hua Lin ◽

Xianqing Zhou ◽

Huixuan Xu ◽

...

Keyword(s):

Posttranslational Modification ◽

Mononuclear Cells ◽

Regulatory Element ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Control Group ◽

Lipocalin 2 ◽

Peripheral Blood Mononuclear ◽

Modified Proteins ◽

Protein Posttranslational Modification

Abstract Background Protein posttranslational modification is an indispensable regulatory element that can fine-tune protein functions and regulate diverse cellular processes. Lysine 2-hydroxyisobutyrylation (Khib) is a protein posttranslational modification that was recently identified and is thought to play a role in a wide variety of active cellular functions. Methods In this report, for the first time, we comparatively studied the 2-hydroxyisobutyrylation proteome in peripheral blood mononuclear cells from a biopsy-proven immunoglobulin A nephropathy (IgAN) group and a normal control group based on liquid chromatography-tandem mass spectrometry. Results Altogether, 7405 proteins were identified and added to a Khib library. Of these proteins, we identified 111 with upregulated expression and 83 with downregulated expression. Furthermore, we identified 428 Khib modification sites on 290 Khib-modified proteins, including 171 sites with increased modification on 122 Khib-modified proteins and 257 specific sites with reduced modification on 168 Khib-modified proteins. Conclusions Importantly, the abundance of lipocalin 2 was increased in the differentially expressed proteins, and a KEGG-based functional enrichment analysis showed that Khib proteins clustered in the IL-17 signaling pathway and phagosome category, which may have important associations with IgAN. Our data enlighten our understanding of Khib in IgAN and indicate that Khib may have important regulatory roles in IgAN.

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