Characterization of the amino acid response element within the human sodium-coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene
- 11 April 2006
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 395 (3), 517-527
- https://doi.org/10.1042/bj20051867
Abstract
The neutral amino acid transport activity, System A, is enhanced by amino acid limitation of mammalian cells. Of the three gene products that encode System A activity, the one that exhibits this regulation is SNAT2 (sodium-coupled neutral amino acid transporter 2). Fibroblasts that are deficient in the amino acid response pathway exhibited little or no induction of SNAT2 mRNA. Synthesis of SNAT2 mRNA increased within 1–2 h after amino acid removal from HepG2 human hepatoma cells. The amino acid responsive SNAT2 genomic element that mediates the regulation has been localized to the first intron. Increased binding of selected members of the ATF (activating transcription factor) and C/EBP (CCAAT/enhancer-binding protein) families to the intronic enhancer was established both in vitro and in vivo. In contrast, there was no significant association of these factors with the SNAT2 promoter. Expression of exogenous individual ATF and C/EBP proteins documented that specific family members are associated with either activation or repression of SNAT2 transcription. Chromatin immunoprecipitation analysis established in vivo that amino acid deprivation led to increased RNA polymerase II recruitment to the SNAT2 promoter.Keywords
This publication has 39 references indexed in Scilit:
- Interaction of RNA-binding Proteins HuR and AUF1 with the Human ATF3 mRNA 3′-Untranslated Region Regulates Its Amino Acid Limitation-induced StabilizationPublished by Elsevier BV ,2005
- Transcriptional control of cystine/glutamate transporter gene by amino acid deprivationBiochemical and Biophysical Research Communications, 2004
- Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cellsProceedings of the National Academy of Sciences, 2004
- Induction of CHOP Expression by Amino Acid Limitation Requires Both ATF4 Expression and ATF2 PhosphorylationJournal of Biological Chemistry, 2004
- Transcriptional Control of the Human Sodium-coupled Neutral Amino Acid Transporter System A Gene by Amino Acid Availability Is Mediated by an Intronic ElementJournal of Biological Chemistry, 2004
- Characterization of the nutrient-sensing response unit in the human asparagine synthetase promoterBiochemical Journal, 2003
- Differences in the Molecular Mechanisms Involved in the Transcriptional Activation of the CHOP and Asparagine Synthetase Genes in Response to Amino Acid Deprivation or Activation of the Unfolded Protein ResponsePublished by Elsevier BV ,2002
- ATF4 Is a Mediator of the Nutrient-sensing Response Pathway That Activates the Human Asparagine Synthetase GeneJournal of Biological Chemistry, 2002
- Activation of the Human Asparagine Synthetase Gene by the Amino Acid Response and the Endoplasmic Reticulum Stress Response Pathways Occurs by Common Genomic ElementsJournal of Biological Chemistry, 2000
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976