Glycosylation is a novel TGFβ1-independent post-translational modification of Smad2

Gotoh, Tadao; Iwahana, Hiroyuki; Kannan, Surya; Marei, Reham Ghazal; Mousa, Hanaa; El‐Gamal, Mahmoud A.; Souchelnytskyi, Serhiy

doi:10.1016/j.bbrc.2019.11.039

Cited by 8 publications

(3 citation statements)

References 24 publications

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“…TGFβ activates Smad transcription factors leading to the transcription of EMT-related genes. SMAD2 and SMAD4 have been reported to be modified by O-GlcNAc, 62,79 and, in the case of SMAD4, this modification prevents proteasomal degradation by blocking interaction and phosphorylation of SMAD4 by glycogen kinase-3β (GSK3β), increasing SMAD4 half-life and transcriptional activity. 80 Often one can find various combinations or all forms of aberrant glycosylation on specific proteins important for proper cell growth and death.…”

Section: Glycosylation In Diseasementioning

confidence: 99%

Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery

Doud

Yeh

2023

Technol Cancer Res Treat

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Glycosylation has a clear role in cancer initiation and progression, with numerous studies identifying distinct glycan features or specific glycoproteoforms associated with cancer. Common findings include that aggressive cancers tend to have higher expression levels of enzymes that regulate glycosylation as well as glycoproteins with greater levels of complexity, increased branching, and enhanced chain length1. Research in cancer glycoproteomics over the last 50-plus years has mainly focused on technology development used to observe global changes in glycosylation. Efforts have also been made to connect glycans to their protein carriers as well as to delineate the role of these modifications in intracellular signaling and subsequent cell function. This review discusses currently available techniques utilizing mass spectrometry-based technologies used to study glycosylation and highlights areas for future advancement.

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Section: Glycosylation In Diseasementioning

confidence: 99%

Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery

Doud

Yeh

2023

Technol Cancer Res Treat

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“…Thus, for example, the rLcc9 laccase from Coprinopsis cinerea expressed in Pichia pastoris and three mutant proteins have given masses of 60.19, 59.99, 57.24, and 59.34 kDa, respectively by MALDI‐TOF. These masses indicated that at least two of the potential glycosylation sites were decorated with high‐mannose‐type glycans (Xu, Wu, et al, 2019) Glycosylation ( N ‐GlcNAc and O ‐Man) of the lytic polysaccharide monooxygenase Ls AA9B) has also been suspected following a mass measurement (23.255 Da) (Frandsen et al, 2019) and the method has also been used for glycopeptides following trypsin digestion as shown for the protein Smad2 (Gotoh et al, 2020). The scavenger receptor SR‐F1 has a measured mass of 49.1 ± 0.4 kDa as determined by MALDI‐TOF MS from sinapinic acid.…”

Section: Studies On Specific Carbohydrate Typesmentioning

confidence: 99%

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2019–2020

Harvey

2023

Mass Spectrometry Reviews

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This review is the tenth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2020. Also included are papers that describe methods appropriate to analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. The review is basically divided into three sections: (1) general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation, quantification and the use of arrays. (2) Applications to various structural types such as oligo‐ and polysaccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals, and (3) other areas such as medicine, industrial processes and glycan synthesis where MALDI is extensively used. Much of the material relating to applications is presented in tabular form. The reported work shows increasing use of incorporation of new techniques such as ion mobility and the enormous impact that MALDI imaging is having. MALDI, although invented nearly 40 years ago is still an ideal technique for carbohydrate analysis and advancements in the technique and range of applications show little sign of diminishing.

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“…Following the activation of TGF-β1 receptors, phosphorylated Smad2/3 (p-Smad2/3) translocates to the nucleus from the cytoplasm, governing the transcription of fibrogenic genes [ 16 , 19 , 20 ]. The stability and activity of TGF-β1 signaling components are reportedly significantly influenced by posttranslational modifications, especially ubiquitination [ 21 , 22 , 23 , 24 ]. NEDD4L, an E3 ubiquitin ligase, has been recognized as the primary ubiquitin ligase for the degradation of p-Smad2/3 [ 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3

Wang,

Li,

Guan

et al. 2024

IJMS

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Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells’ (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-β1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.

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Glycosylation is a novel TGFβ1-independent post-translational modification of Smad2

Cited by 8 publications

References 24 publications

Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery

Mass Spectrometry-Based Glycoproteomic Workflows for Cancer Biomarker Discovery

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2019–2020

The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3

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