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PMID:10085239

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Citation

Barbosa-Tessmann, IP, Pineda, VL, Nick, HS, Schuster, SM and Kilberg, MS (1999) Transcriptional regulation of the human asparagine synthetase gene by carbohydrate availability. Biochem. J. 339 ( Pt 1):151-8

Abstract

Transcription of the asparagine synthetase (AS) gene is induced by amino acid deprivation. The present data illustrate that this gene is also under transcriptional control by carbohydrate availability. Incubation of human HepG2 hepatoma cells in glucose-free medium resulted in an increased AS mRNA content, reaching a maximum of about 14-fold over control cells after approx. 12 h. Extracellular glucose caused the repression of the content of AS mRNA in a concentration-dependent manner, with a k1/2 (concentration causing a half-maximal repression) of 1 mM. Fructose, galactose, mannose, 2-deoxyglucose and xylitol were found to maintain the mRNA content of both AS and the glucose-regulated protein GRP78 in a state of repression, whereas 3-O-methylglucose did not. Incubation in either histidine-free or glucose-free medium also resulted in adaptive regulation of the AS gene in BNL-CL.2 mouse hepatocytes, rat C6 glioma cells and human MOLT4 lymphocytes, in addition to HepG2 cells. In contrast, the steady-state mRNA content of GRP78 was unaffected by amino acid availability. Transient transfection assays using a reporter gene construct documented that glucose deprivation increases AS gene transcription via elements within the proximal 3 kbp of the AS promoter. These results illustrate that human AS gene transcription is induced following glucose limitation of the cells.

Links

PubMed PMC1220139

Keywords

Animals; Aspartate-Ammonia Ligase/genetics; Base Sequence; Cell Line; DNA Primers; Gene Expression Regulation, Enzymologic/drug effects; Glucose/pharmacology; Humans; Mice; Promoter Regions, Genetic; RNA, Messenger/genetics; Rats; Transcription, Genetic/drug effects

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ASNS

involved_in

GO:0042149: cellular response to glucose starvation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:ASNS

involved_in

GO:0042149: cellular response to glucose starvation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:BIP

involved_in

GO:0042149: cellular response to glucose starvation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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