Hyper-&lt;i&gt;O&lt;/i&gt;-GlcNAcylation Inhibits the Induction of Heat Shock Protein 70 (Hsp 70) by Sodium Arsenite in HeLa Cells

Miura, Yuri; Sato, Takatoshi; Sakurai, Yoko; Sakai, Ryo; Hiraoka, Wakako; Endo, Tamao

doi:10.1248/bpb.b14-00170

Cited by 2 publications

(1 citation statement)

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“…[ 41 ] In addition, the work by Miura suggested that O‐GlcNAcylation did not regulate the nuclear translocation and phosphorylation of heat shock Factor 1. [ 85 ] It is therefore plausible that O‐GlcNAc modulates protein nucleocytoplasmic shuttling in many ways, including through changing protein conformation, [ 86 ] activating complex signaling pathways, [ 87 ] and generating extensive crosstalk with other posttranscriptional modifications. [ 88 , 89 ] The need for a better understanding of the functions and mechanisms of O‐GlcNAcylation remains.…”

Section: Discussionmentioning

confidence: 99%

Bladder Cancer‐Derived Small Extracellular Vesicles Promote Tumor Angiogenesis by Inducing HBP‐Related Metabolic Reprogramming and SerRS O‐GlcNAcylation in Endothelial Cells

Peng

Zhang

et al. 2022

Advanced Science

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A malformed tumour vascular network provokes the nutrient-deprived tumour microenvironment (TME), which conversely activates endothelial cell (EC) functions and stimulates neovascularization. Emerging evidence suggests that the flexible metabolic adaptability of tumour cells helps to establish a metabolic symbiosis among various cell subpopulations in the fluctuating TME. In this study, the authors propose a novel metabolic link between bladder cancer (BCa) cells and ECs in the nutrient-scarce TME, in which BCa-secreted glutamine-fructose-6-phosphate aminotransferase 1 (GFAT1) via small extracellular vesicles (sEVs) reprograms glucose metabolism by increasing hexosamine biosynthesis pathway flux in ECs and thus enhances O-GlcNAcylation. Moreover, seryl-tRNA synthetase (SerRS) O-GlcNAcylation at serine 101 in ECs promotes its degradation by ubiquitination and impeded importin 𝜶5-mediated nuclear translocation. Intranuclear SerRS attenuates vascular endothelial growth factor transcription by competitively binding to the GC-rich region of the proximal promotor. Additionally, GFAT1 knockout in tumour cells blocks SerRS O-GlcNAcylation in ECs and attenuates angiogenesis both in vitro and in vivo. However, administration of GFAT1-overexpressing BCa cells-derived sEVs increase the angiogenetic activity in the ECs of GFAT1-knockout mice. In summary, this study suggests that inhibiting sEV-mediated GFAT1 secretion from BCa cells and targeting SerRS O-GlcNAcylation in ECs may serve as novel strategies for BCa antiangiogenetic therapy.

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