Identification of Posttranslational Modifications (PTMs) of Proteins by Mass Spectrometry

Aslebagh, Roshanak; Wormwood, Kelly L.; Channaveerappa, Devika; Wetie, Armand G. Ngounou; Woods, Alisa G.; Darie, Costel C.

doi:10.1007/978-3-030-15950-4_11

Cited by 33 publications

(26 citation statements)

References 107 publications

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“…Many of these are enzymes, and therefore contribute to the human metabolome, either through the metabolism of a single specific metabolite or pair of metabolites, such as lactate dehydrogenase or in a pleiotropic fashion, such as the thousands of potential metabolites produced by the human cytochromes P450 [29]. Nevertheless, it has been estimated that there are 1-2 million "protein entities" that are expressed in a cell at a given time as a result of posttranslational modifications (PTMs), such as acetylation, phosphorylation, and glycosylation [30].…”

Section: The Need For Biomarkers Of Premalignant Liver Diseasementioning

confidence: 99%

“…These findings cannot be considered as biomarkers of severe CLF, as they are not specific. A Chinese study in compensated cirrhosis (30), decompensated cirrhosis (30), and healthy controls (30) using 1 H NMR on serum samples reported that succinate, pyruvate, and phenylalanine increased with cirrhosis progression [153]. Yet, again, these cannot be considered as biomarkers due to their lack of specificity.…”

Section: Fibrosis and Cirrhosismentioning

confidence: 99%

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Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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Section: The Need For Biomarkers Of Premalignant Liver Diseasementioning

confidence: 99%

Section: Fibrosis and Cirrhosismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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“…Over the last years, mass spectrometry (MS)-based proteomic methods have significantly advanced with respect to their robustness, performance, and scope 2 . With time, methods have been developed, which measure functionally important properties of proteins such as the modification state 3 as well as the composition and topology of protein complexes 4 in addition to the presence and abundance of a protein in a sample. In combination, these MS techniques constitute a powerful tool set to measure mechanistically relevant responses of the cell to (genomic) perturbations.…”

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confidence: 99%

Multi-layered proteomic analyses decode compositional and functional effects of cancer mutations on kinase complexes

et al. 2020

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Rapidly increasing availability of genomic data and ensuing identification of disease associated mutations allows for an unbiased insight into genetic drivers of disease development. However, determination of molecular mechanisms by which individual genomic changes affect biochemical processes remains a major challenge. Here, we develop a multilayered proteomic workflow to explore how genetic lesions modulate the proteome and are translated into molecular phenotypes. Using this workflow we determine how expression of a panel of disease-associated mutations in the Dyrk2 protein kinase alter the composition, topology and activity of this kinase complex as well as the phosphoproteomic state of the cell. The data show that altered protein-protein interactions caused by the mutations are associated with topological changes and affected phosphorylation of known cancer driver proteins, thus linking Dyrk2 mutations with cancer-related biochemical processes. Overall, we discover multiple mutation-specific functionally relevant changes, thus highlighting the extensive plasticity of molecular responses to genetic lesions.

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“…Posttranslational modifications (PTMs) refer to various changes occurred at the polypeptide chain of proteins, including alterations by proteolytic cleavage, formation of disulfide bonds or covalent attachment of phosphate, sulfate, alkyl groups, lipids, carbohydrates, polypeptides and others ( Aslebagh et al. 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Posttranslational Modifications: Regulation of Nitrogen Utilization and Signaling

Wang

Zhang

et al. 2021

Plant and Cell Physiology

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Nitrogen is the most important macroelement required for the composition of key molecules, such as nucleic acids, proteins and other organic compounds. As sessile organisms, plants have evolved sophisticated mechanisms to acquire nitrogen for their normal growth and development. Besides transcriptional and translational regulation of nitrogen uptake, assimilation, remobilization, and signal transduction, post-translational modifications (PTMs) are also shown to participate in these processes in plants. In addition to alterations in protein abundance, PTMs may dramatically increase the complexity of the proteome without the concomitant changes in gene transcription, and have emerged as an important type of protein regulation in terms of protein function, subcellular localization, and protein activity and stability. Herein, we briefly summarize recent advances on the post-translational regulation of nitrogen uptake, assimilation, remobilization, and nitrogen signaling, and discuss the underlying mechanisms of PTMs as well as the signal output of such PTMs. Understanding these regulation mechanisms will provide novel insights for improving nitrogen use efficiency of plants.

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Identification of Posttranslational Modifications (PTMs) of Proteins by Mass Spectrometry

Cited by 33 publications

References 107 publications

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Multi-layered proteomic analyses decode compositional and functional effects of cancer mutations on kinase complexes

Posttranslational Modifications: Regulation of Nitrogen Utilization and Signaling

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