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PMID: 16445384 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Characterization of the amino acid response element within the human sodium-coupled neutral amino acid transporter 2 (SNAT2) System A transporter gene.

The Biochemical journal ·Vol. 395 ·No. 3 ·2006-05-01 ·Pages 517-27

Palii SS, Thiaville MM, Pan YX, Zhong C, Kilberg MS

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.

MeSH Terms
Activating Transcription Factors/genetics,metabolism Amino Acid Transport System A/genetics,metabolism Amino Acids/pharmacology Animals Base Sequence CCAAT-Enhancer-Binding Proteins/genetics,metabolism Cell Line DNA/genetics,metabolism Dimerization Eukaryotic Initiation Factor-2/metabolism Gene Expression Regulation/drug effects Genome, Human/genetics Humans Mice Molecular Sequence Data Promoter Regions, Genetic/genetics Protein Binding Protein Kinases/metabolism Protein Serine-Threonine Kinases RNA, Messenger/genetics Response Elements/genetics Sodium/metabolism Transcription, Genetic/drug effects,genetics
Chemicals
Activating Transcription Factors Amino Acid Transport System A Amino Acids CCAAT-Enhancer-Binding Proteins Eukaryotic Initiation Factor-2 RNA, Messenger SLC38A2 protein, human DNA Sodium Protein Kinases Eif2ak4 protein, mouse Protein Serine-Threonine Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Palii Stela S
Department of Biochemistry and Molecular Biology, Shands Cancer Center, and the Genetics Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA.
Thiaville Michelle M
Pan Yuan-Xiang
Zhong Can
Kilberg Michael S
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
1470-8728
DOI
10.1042/BJ20051867
Published
2006-05-01
Pages
517-27
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1462688
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052064 · United States
NCI NIH HHS · T32 CA009126 · United States
NIDDK NIH HHS · DK-52064 · United States
NCI NIH HHS · T32-CA009126 · United States
External Links
PubMed source DOI: 10.1042/BJ20051867 PMC Full Text View journal details
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