SECRET AGENT O-GlcNAcylates Hundreds of Proteins Involved in Diverse Cellular Processes in Arabidopsis DOI Creative Commons
Ruben Shrestha, Sumudu Karunadasa, TaraBryn S Grismer

et al.

Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: 23(4), P. 100732 - 100732

Published: Feb. 8, 2024

O-GlcNAcylation is a critical post-translational modification of proteins observed in both plants and animals plays key role growth development. While considerable knowledge exists about over 3000 substrates animals, our understanding this remains limited. Unlike possess two putative homologs: SECRET AGENT (SEC) SPINDLY (SPY), with SPY also exhibiting O-fucosylation activity. To investigate SEC's as major O-GlcNAc transferase plants, we utilized LWAC enrichment SILIA labeling, quantifying at MS1 MS2 levels. Our findings reveal significant reduction levels the sec mutant, indicating mediating O-GlcNAcylation. Through comprehensive approach, combining HCD EThcD fragmentation substantial fractionations, expanded GlcNAc profiling, identifying 436 targets, including 227 new targets. The targets span diverse cellular processes, suggesting broad regulatory functions enabled exploration crosstalk between O-fucosylation. We examined for site assignment. This report advances facilitating further research field.

Language: Английский

dbPTM in 2022: an updated database for exploring regulatory networks and functional associations of protein post-translational modifications DOI Creative Commons
Zhongyan Li, Shangfu Li, Mengqi Luo

et al.

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 50(D1), P. D471 - D479

Published: Oct. 13, 2021

Protein post-translational modifications (PTMs) play an important role in different cellular processes. In view of the importance PTMs functions and massive data accumulated by rapid development mass spectrometry (MS)-based proteomics, this paper presents update dbPTM with over 2 777 000 PTM substrate sites obtained from existing databases manual curation literature, which more than 235 entries are experimentally verified. This has manually curated 42 new modification types that were not included previous version. Due to increasing number studies on mechanism past few years, a great deal upstream regulatory proteins have been revealed. The updated thus collates information merges them into protein-protein interaction network. To enhance understanding association between molecular functions/cellular processes, functional annotations integrated database. addition, PTM-related resources, including annotation prediction tools also renewed. Overall, update, we would like provide users most abundant comprehensive proteins. is now freely accessible at https://awi.cuhk.edu.cn/dbPTM/.

Language: Английский

Citations

125
Targeting USP8 Inhibits O‐GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT DOI Creative Commons
Jianing Tang,

Guo Long,

Kuan Hu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(33)

Published: Oct. 22, 2023

Hepatocellular carcinoma (HCC) is a lethal and aggressive human malignancy. The present study examins the anti-tumor effects of deubiquitylating enzymes (DUB) inhibitors in HCC. It found that inhibitor ubiquitin specific peptidase 8 (USP8) DUB-IN-3 shows most effective anti-cancer responses. Targeting USP8 inhibits proliferation HCC induces cell ferroptosis. In vivo xenograft metastasis experiments indicate inhibition suppresses tumor growth lung metastasis. treatment or depletion decrease intracellular cystine levels glutathione biosynthesis while increasing accumulation reactive oxygen species (ROS). Mechanistical studies reveal stabilizes O-GlcNAc transferase (OGT) via inhibiting K48-specific poly-ubiquitination process on OGT protein at K117 site, STE20-like kinase (SLK)-mediated S716 phosphorylation required for interaction with OGT. Most importantly, O-GlcNAcylates solute carrier family 7, member 11 (SLC7A11) Ser26 cells, which essential SLC7A11 to import from extracellular environment. Collectively, this demonstrates pharmacological knockout can inhibit progression induce ferroptosis decreasing stability OGT, imposes great challenge targeting potential approach treatment.

Language: Английский

Citations

44
O-GlcNAcylation in cancer development and immunotherapy DOI

Xue-Fen He,

Xiaoli Hu,

Gao-Jing Wen

et al.

Cancer Letters, Journal Year: 2023, Volume and Issue: 566, P. 216258 - 216258

Published: June 4, 2023

Language: Английский

Citations

43
O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology DOI Creative Commons
Aaron T. Balana, Anne‐Laure Mahul‐Mellier, Binh A. Nguyen

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(5), P. 646 - 655

Published: Feb. 12, 2024

Abstract Amyloid-forming proteins such α-synuclein and tau, which are implicated in Alzheimer’s Parkinson’s disease, can form different fibril structures or strains with distinct toxic properties, seeding activities pathology. Understanding the determinants contributing to formation of amyloid features could open new avenues for developing disease-specific diagnostics therapies. Here we report that O-GlcNAc modification monomers results core structure, as revealed by cryogenic electron microscopy, diminished activity seeding-based neuronal rodent models disease. Although mechanisms underpinning neutralization O-GlcNAc-modified fibrils remain unclear, our vitro mechanistic studies indicate heat shock interactions inhibit their activity, suggesting may alter interactome ways lead reduce vivo. Our show posttranslational modifications, modification, key pathogenicity.

Language: Английский

Citations

28
O-GlcNAcAtlas: A database of experimentally identified O-GlcNAc sites and proteins DOI
Junfeng Ma, Yaoxiang Li, Chunyan Hou

et al.

Glycobiology, Journal Year: 2021, Volume and Issue: 31(7), P. 719 - 723

Published: Jan. 5, 2021

O-linked β-N-acetylglucosamine (O-GlcNAc) is a post-translational modification (i.e., O-GlcNAcylation) on the serine/threonine residues of proteins. As unique intracellular monosaccharide modification, protein O-GlcNAcylation plays important roles in almost all biochemical processes examined. Aberrant underlies etiologies number chronic diseases. With tremendous improvement techniques, thousands proteins along with their O-GlcNAc sites have been reported. However, until now, there are few databases dedicated to accommodate rapid accumulation such information. Thus, O-GlcNAcAtlas created integrate experimentally identified and consists two datasets (Dataset-I Dataset-II, for unambiguously ambiguously sites, respectively), representing total 4571 modified from species studied 1984 31 Dec 2019. For each protein, comprehensive information (including species, sample type, gene symbol, peptides and/or site mapping methods literature references) provided. To solve heterogeneity among data collected different sources, sequence identity these reported mapped UniProtKB entries. our knowledge, highly rigorously curated database encapsulating past 35 years. We expect that will be useful resource facilitate studies computational analyses O-GlcNAcylation. The public version web interface can found at http://oglcnac.org/.

Language: Английский

Citations

79
High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism DOI Open Access

Yuning Pang,

Xiang Xu, Xiaojun Xiang

et al.

Nutrients, Journal Year: 2021, Volume and Issue: 13(6), P. 1740 - 1740

Published: May 21, 2021

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, mechanism of liver induced by high is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) explore fat. In present study, ORF ACC1 ACC2 were cloned characterized. Meanwhile, mRNA protein increased in fed with a (HFD) or hepatocytes incubated oleic acid (OA). The phosphorylation ACC was also decreased OA. Moreover, AICAR dramatically improved ACC, OA significantly inhibited AMPK/ACC pathway. Further experiments showed that global O-GlcNAcylation agonist AMPK ACC. Importantly, disorder lipid metabolism caused HFD could be rescued treating CP-640186, dual inhibitor ACC2. These observations suggested may activate affect pathway regulate synthesis, emphasized importance role homeostasis.

Language: Английский

Citations

64
Metabolic glycoengineering – exploring glycosylation with bioorthogonal chemistry DOI
Markus Kufleitner, Lisa Maria Haiber, Valentin Wittmann

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 52(2), P. 510 - 535

Published: Dec. 20, 2022

Metabolic glycoengineering in combination with bioorthogonal chemistry provides a means to study and exploit the biological functions of glycans.

Language: Английский

Citations

63
Demystifying the O-GlcNAc Code: A Systems View DOI
Junfeng Ma, Chunyan Hou,

Ci Wu

et al.

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(20), P. 15822 - 15864

Published: March 18, 2022

Post-translational modification with O-linked β-N-acetylglucosamine (O-GlcNAc), a process referred to as O-GlcNAcylation, occurs on vast variety of proteins. Mounting evidence in the past several decades has clearly demonstrated that O-GlcNAcylation is unique and ubiquitous modification. Reminiscent code, protein functions crucial regulator nearly all cellular processes studied. The primary aim this review summarize developments our understanding myriad substrates modified by from systems perspective. Specifically, we provide comprehensive survey multiple species studied, including eukaryotes (e.g., protists, fungi, plants, Caenorhabditis elegans, Drosophila melanogaster, murine, human), prokaryotes, some viruses. We evaluate features structural properties sequence motifs) O-GlcNAc proteins across species. Given species-, tissue-/cell-, protein-, site-specific manner, discuss functional roles human focus particularly classes relatively well-characterized (including transcription factors, kinases, phosphatases, E3 ubiquitin-ligases), representative presented. hope view great endeavor 35 years will help demystify code lead more fascinating studies come.

Language: Английский

Citations

58
SDNN-PPI: self-attention with deep neural network effect on protein-protein interaction prediction DOI Creative Commons
Xue Li, Peifu Han, Wang Gan

et al.

BMC Genomics, Journal Year: 2022, Volume and Issue: 23(1)

Published: June 27, 2022

Protein-protein interactions (PPIs) dominate intracellular molecules to perform a series of tasks such as transcriptional regulation, information transduction, and drug signalling. The traditional wet experiment method obtain PPIs is costly time-consuming.

Language: Английский

Citations

57
Tools for mammalian glycoscience research DOI Creative Commons
Matthew E. Griffin, Linda C. Hsieh‐Wilson

Cell, Journal Year: 2022, Volume and Issue: 185(15), P. 2657 - 2677

Published: July 1, 2022

Language: Английский

Citations

44