The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase

Perry J. Bain, Rene Leblanc-Chaffin, Hong Chen, Stela S. Palii, Kelly M. Leach, Michael S. Kilberg

Research output: Contribution to journalArticle

Abstract

After amino acid deprivation, the mRNA content for both asparagine synthetase (AS) and the system A transporter ATA2 is increased. The purpose of the reported experiments was to characterize the molecular mechanism for the ATA2 gene and to contrast the ATA2 regulatory characteristics with those of AS. Amino acid limitation was initiated by incubation of HepG2 human hepatoma cells in either amino acid-free Krebs-Ringer bicarbonate buffer or culture medium lacking the single amino acid histidine. For ATA2, like AS, the elevated mRNA content was due to increased transcription. However, there were fundamental differences between the mechanisms for nutrient regulation of the AS and ATA2 genes. When cells were deprived of amino acids, there was a lag period of ∼4′ h before an increase in AS mRNA occurred, whereas the elevation of ATA2 mRNA was readily detectable at 2-4 h. Consistent with these observations, de novo protein synthesis was absolutely required for the activation of the AS gene, but the increase in ATA2 mRNA was largely independent of protein synthesis. Furthermore, in contrast to AS, transcription from the ATA2 gene was not increased by glucose deprivation. Given this lack of ATA2 transcriptional activation by glucose starvation and that the induction of the AS gene by glucose or amino acid starvation is mediated by common genomic elements, it is likely that the ATA2 gene does not contain the same genomic amino acid-responsive cis-elements as the AS gene.

Original languageEnglish (US)
Pages (from-to)3023-3029
Number of pages7
JournalJournal of Nutrition
Volume132
Issue number10
StatePublished - Oct 1 2002
Externally publishedYes

Fingerprint

Aspartate-Ammonia Ligase
aspartate-ammonia ligase
Amino Acid Transport Systems
transcriptional activation
Transcriptional Activation
transporters
amino acids
Amino Acids
Genes
genes
Messenger RNA
Starvation
Glucose
glucose
starvation
Amino Acid Transport System A
transcription (genetics)
protein synthesis
genomics
hepatoma

Keywords

  • Gene expression
  • Metabolite control
  • Nutrient control
  • Transcription

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase. / Bain, Perry J.; Leblanc-Chaffin, Rene; Chen, Hong; Palii, Stela S.; Leach, Kelly M.; Kilberg, Michael S.

In: Journal of Nutrition, Vol. 132, No. 10, 01.10.2002, p. 3023-3029.

Research output: Contribution to journalArticle

Bain, Perry J. ; Leblanc-Chaffin, Rene ; Chen, Hong ; Palii, Stela S. ; Leach, Kelly M. ; Kilberg, Michael S. / The mechanism for transcriptional activation of the human ATA2 transporter gene by amino acid deprivation is different than that for asparagine synthetase. In: Journal of Nutrition. 2002 ; Vol. 132, No. 10. pp. 3023-3029.
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