Abstract
Increased levels of N-linked (β-N- acetylglucosamine)2 [N-GlcNAc2]-modified proteins have been recognized to be an effective response to glucose deprivation. In the first step of this study, using a next generation sequencer, we investigated the global transcriptional changes induced by glucose deprivation in a T24 bladder carcinoma cell line, producing N-GlcNAc2-modified proteins under glucose deprivation. Our transcriptome analysis revealed significant up-regulation of the UDP-GlcNAc biosynthesis pathway and unfolded protein response genes, and down-regulation of G2/M transition-related genes containing mitotic kinases. Our biological analysis confirmed that N-GlcNAc2-modified proteins were localized with BiP proteins in the ER. G2/M arrest was caused by glucose deprivation in T24 cells. Moreover, the knockdown of unfolded protein response genes induced the expressional recovery of mitotic kinases under glucose deprivation. Taken together, our results suggest N-GlcNAc2-modified proteins produced under glucose deprivation caused unfolded protein response in the ER, and that this response induced G2/M arrest.
Highlights
Glucose metabolism supplies the cell with energy and furnishes carbon skeletons for biosynthesis
We have demonstrated that N-GlcNAc2-modified glycoproteins are induced under glucose deprivation and that they cross-react with the O-GlcNAc-specific antibody CTD110.6 [9]
We found that glucose deprivation up-regulated UDPGlcNAc biosynthesis, and accumulation of N-GlcNAc2-modified proteins caused an unfolded protein response (UPR) in the endoplasmic reticulum (ER)
Summary
Glucose metabolism supplies the cell with energy and furnishes carbon skeletons for biosynthesis. The HBP produces uridine 59-diphospho-N-acetylglucosamine (UDPGlcNAc) [1], which is required for N-glycosylation in the endoplasmic reticulum (ER), N-glycan branching in the Golgi apparatus, and O-linked b-N- acetylglucosamine (O-GlcNAc) modification of proteins in the nucleus, cytoplasm and mitochondria. O-GlcNAc-modification of proteins is a feature of many cellular responses to the nutritional state of the cell as well as to stress [2,3,4]. We have demonstrated that N-GlcNAc2-modified glycoproteins are induced under glucose deprivation and that they cross-react with the O-GlcNAc-specific antibody CTD110.6 [9]. It is speculated that immature N-linked glycoproteins formed as a result of abundant N-GlcNAc2-modified proteins is a novel pathway activated in response to glucose deprivation for efficient utilization of this carbon source
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