Amino Acids

, Volume 37, Issue 1, pp 79–88

Specificity of amino acid regulated gene expression: analysis of genes subjected to either complete or single amino acid deprivation

  • S. S. Palii
  • C. E. Kays
  • C. Deval
  • A. Bruhat
  • P. Fafournoux
  • M. S. Kilberg
Original Article

Abstract

Amino acid deprivation activates the amino acid response (AAR) pathway that enhances transcription of genes containing an amino acid response element (AARE). The present data reveal a quantitative difference in the response to deprivation of individual amino acids. The AAR leads to increased eukaryotic initiation factor 2α (eIF2α) phosphorylation and ATF4 translation. When HepG2 cells were deprived of an individual essential amino acid, p-eIF2α and activating transcription factor 4 were increased, but the correlation was relatively weak. Complete amino acid starvation in either Earle’s balanced salt solution or Krebs–Ringer bicarbonate buffer (KRB) resulted in activation of transcription driven by a SNAT2 genomic fragment that contained an AARE. However, for the KRB, a proportion of the transcription was AARE-independent suggesting that amino acid-independent mechanisms were responsible. Therefore, activation of AARE-driven transcription is triggered by a deficiency in any one of the essential amino acids, but the response is not uniform. Furthermore, caution must be exercised when using a medium completely devoid of amino acids.

Keywords

SNAT2 System A Nutrient starvation Amino acid transport ATF4 eIF2 

Abbreviations

AAR

Amino acid response

AARE

Amino acid response element

ASNS

Asparagine synthetase

ATF3

Activating transcription factor 3

ATF4

Activating transcription factor 4

C/EBPβ

CCAAT/enhancer-binding protein beta

CAT-1

Cationic amino acid transporter

CHOP

C/EBP homology protein

EAA

Essential amino acids

EBSS

Earle’s balanced salt solution

eIF2

Eukaryotic initiation factor 2

GCN2

General control non-derepressible

KRB

Krebs–Ringer bicarbonate buffer

MEM

Minimal essential medium

qPCR

Quantitative real-time PCR

RT-PCR

Reverse transcriptase-polymerase chain reaction

SNAT2

System A sodium-dependent neutral amino acid transporter 2

VEGF

Vascular endothelial growth factor

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • S. S. Palii
    • 1
  • C. E. Kays
    • 1
  • C. Deval
    • 2
  • A. Bruhat
    • 2
  • P. Fafournoux
    • 2
  • M. S. Kilberg
    • 1
  1. 1.Department of Biochemistry and Molecular Biology, Genetics Institute, Shands Cancer Center and Center for Nutritional SciencesUniversity of Florida, College of MedicineGainesvilleUSA
  2. 2.Unité de Nutrition Humaine, équipe Genes-NutrimentsINRA de Clermont-TheixSaint Genès ChampanelleFrance

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