Emerging roles of O-GlcNAcylation in protein trafficking and secretion

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(3), P. 105677 - 105677

Published: Jan. 23, 2024

The emerging roles of O-GlcNAcylation, a distinctive post-translational modification, are increasingly recognized for their involvement in the intricate processes protein trafficking and secretion. This modification exerts its influence on both conventional unconventional secretory pathways. Under healthy stress conditions, such as during diseases, it orchestrates transport proteins within cells, ensuring timely delivery to intended destinations. O-GlcNAcylation occurs key factors, like coat complexes (COPI COPII), clathrin, SNAREs (soluble N-ethylmaleimide-sensitive factor attachment receptors), GRASP55 (Golgi reassembly stacking 55 kDa) that control vesicle budding fusion anterograde retrograde understanding offers valuable insights into critical functions cellular physiology progression including neurodegeneration, cancer, metabolic disorders. In this review, we summarize discuss latest findings elucidating O-GlcNAc significance various human

Language: Английский

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Glycosylated nanoplatforms: From glycosylation strategies to implications and opportunities for cancer theranostics

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 371, P. 158 - 178

Published: May 29, 2024

Language: Английский

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Targeting O-GlcNAcylation in cancer therapeutic resistance: The sugar Saga continues

Cancer Letters, Journal Year: 2024, Volume and Issue: 588, P. 216742 - 216742

Published: Feb. 23, 2024

Language: Английский

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Glycosylation gene expression profiles enable prognosis prediction for colorectal cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 4, 2025

This study developed a prognostic model for patients with colon adenocarcinoma (COAD) based on glycosylation-associated genes. By analyzing TCGA-COAD data, 110 key genes were identified, and incorporating five glycosylation-related was constructed. The exhibits good predictive performance is significantly associated clinical features such as age, N stage, M lymph node count. are involved in various biological processes pathways, influence T cell differentiation, may contribute to CRC development. High-risk show higher degree of immune infiltration. aids the early diagnosis, prognosis assessment, treatment planning CRC, offers direction further research.

Language: Английский

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Overexpression of Fatty Acid Synthase Upregulates Glutamine–Fructose-6-Phosphate Transaminase 1 and O-Linked N-Acetylglucosamine Transferase to Increase O-GlcNAc Protein Glycosylation and Promote Colorectal Cancer Growth

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4883 - 4883

Published: April 30, 2024

Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). synthase (FASN), key enzyme of de novo lipid synthesis, is significantly upregulated CRC, and approaches targeting this are currently being tested multiple clinical trials. However, the mechanisms behind pro-oncogenic action FASN still not completely understood. Here, for first time, we show that overexpression increases expression glutamine–fructose-6-phosphate transaminase 1 (GFPT1) O-linked N-acetylglucosamine transferase (OGT), enzymes involved hexosamine metabolism, level O-GlcNAcylation vitro vivo. Consistently, correlates with GFPT1 OGT human CRC tissues. shRNA-mediated downregulation inhibits cellular proliferation protein vitro, knockdown leads to significant decrease tumor growth metastasis Pharmacological inhibition colony formation cells. In summary, our results well promote progression CRC; biosynthesis pathway could be approach disease.

Language: Английский

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O-GlcNAcylation in tumorigenesis and its implications for cancer therapy

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(9), P. 107709 - 107709

Published: Aug. 22, 2024

O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a dynamic and reversible posttranslational modification that targets serine threonine residues in variety of proteins. Uridine diphospho-N-acetylglucosamine, which synthesized from glucose via the hexosamine biosynthesis pathway, major donor this modification. O-GlcNAc transferase sole enzyme transfers GlcNAc onto protein substrates, while O-GlcNAcase responsible for removing O-GlcNAcylation plays an important role tumorigenesis progression through specific substrates. In review, we discuss tumor-related biological functions summarize recent progress development pharmaceutical options to manipulate proteins as potential anticancer therapies.

Language: Английский

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O-GlcNAcylation: A Major Nutrient/Stress Sensor that Regulates Cellular Physiology

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(9), P. 107635 - 107635

Published: Aug. 5, 2024

Language: Английский

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Cycling Molecular Assemblies for Selective Cancer Cell Golgi Disruption

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 5, 2025

The Golgi apparatus is a critical organelle responsible for intracellular trafficking and signaling, orchestrating essential processes such as protein lipid sorting

Language: Английский

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Evidence for Functional Regulation of the KLHL3/WNK Pathway by O-GlcNAcylation

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

The 42-member Kelch-like (KLHL) protein family are adaptors for ubiquitin E3 ligase complexes, governing the stability of a wide range substrates. KLHL proteins critical maintaining proteostasis in variety tissues and mutated human diseases, including cancer, neurodegeneration, familial hyperkalemic hypertension. However, regulation remains incompletely understood. Previously, we reported that two members, KEAP1 gigaxonin, regulated by O-linked β- N -acetylglucosamine (O-GlcNAc), an intracellular form glycosylation. Interestingly, some ubiquitination targets gigaxonin themselves also O-GlcNAcylated, suggesting multi-level control this post-translational modification may influence many pathways. To test hypothesis, examined KLHL3, which ubiquitinates with-no-lysine (WNK) kinases to modulate downstream ion channel activity. Our biochemical glycoproteomic data demonstrate KLHL3 all four WNK (WNK1-4) O-GlcNAcylated. Moreover, our results suggest O-GlcNAcylation affects WNK4 function both osmolarity ferroptosis, with potential implications ranging from blood pressure neuronal health survival. This work demonstrates functional KLHL3/WNK axis supports broader model O-GlcNAc serving as general regulator signaling proteostasis.

Language: Английский

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Natural products and cancer: The urgent need to bridge the gap between preclinical and clinical research

World Journal of Gastrointestinal Oncology, Journal Year: 2025, Volume and Issue: 17(4)

Published: March 24, 2025

Any new report on the anticancer properties of natural products always awakens satisfaction and hope about role international scientific community in its continuous contributions to human health, particularly when those reports contribute both understanding therapeutics cancer. For many decades, have been pivotal drug discovery programs because they offer a diverse array therapeutic possibilities. Recently, two manuscripts published World Journal Gastrointestinal Oncology added data already extensive body preclinical evidence for resveratrol senegenin, compounds widely present herbal preparations used traditional Chinese medicine. The first one, with comprehensive recognized properties, second shows compelling supporting neuroprotective effects, but emerging activities. Natural become key elements expanding dynamic field discovery. However, urgent collective efforts are still needed bridge gap between clinical research thus bring breakthroughs.

Language: Английский

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