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Nutrient-Gene Interactions

The Mechanism for Transcriptional Activation of the Human ATA2 Transporter Gene by Amino Acid Deprivation is Different than That for Asparagine Synthetase¹

Perry J. Bain, Rene LeBlanc-Chaffin^*, Hong Chen^*, Stela S. Palii^*, Kelly M. Leach^* and Michael S. Kilberg^*2

^* Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610-0245; and the Department of Pathology, School of Veterinary Medicine, University of Georgia, Athens, GA, 30602

²To whom correspondence should be addressed. E-mail: mkilberg{at}ufl.edu.

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.

KEY WORDS: • metabolite control • transcription • nutrient control • gene expression

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