A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation

Alex B. Lopez, Chuanping Wang, Charlie C. Huang, Ibrahim Yaman, Yi Li, Kaushik Chakravarty, Peter F. Johnson, Cheng Ming Chiang, Martin D. Snider, Ronald C. Wek, Maria Hatzoglou

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The adaptive response to amino acid limitation in mammalian cells inhibits global protein synthesis and promotes the expression of proteins that protect cells from stress. The arginine/lysine transporter, cat-1, is induced during amino acid starvation by transcriptional and post-transcriptional mechanisms. It is shown in the present study that the transient induction of cat-1 transcription is regulated by the stress response pathway that involves phosphorylation of the translation initiation factor, eIF2 (eukaryotic initiation factor-2). This phosphorylation induces expression of the bZIP (basic leucine zipper protein) transcription factors C/EBP (CCAAT/enhancer-binding protein)-β and ATF (activating transcription factor) 4, which in turn induces ATF3. Transfection experiments in control and mutant cells, and chromatin immunoprecipitations showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1 gene, which functions both in the endogenous and in a heterologous promoter. ATF4 and C/EBPβ activated transcription when expressed in transfected cells and they bound as heterodimers to the AARE in vitro. The induction of transcription by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with C/EBPβ. These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism.

Original languageEnglish (US)
Pages (from-to)163-173
Number of pages11
JournalBiochemical Journal
Volume402
Issue number1
DOIs
StatePublished - Feb 15 2007

Fingerprint

Transcription
Starvation
Lysine
Arginine
CCAAT-Enhancer-Binding Proteins
Cats
Feedback
Amino Acids
Response Elements
Phosphorylation
Activating Transcription Factor 4
Eukaryotic Initiation Factor-2
Basic-Leucine Zipper Transcription Factors
Leucine Zippers
Peptide Initiation Factors
Proteins
Chromatin Immunoprecipitation
Transcriptional Activation
Chromatin
Transfection

Keywords

  • Activating transcription factor
  • Amino acid response element
  • Amino acid transporter
  • eIF2 phosphorylation
  • Stress response gene
  • Transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Lopez, A. B., Wang, C., Huang, C. C., Yaman, I., Li, Y., Chakravarty, K., ... Hatzoglou, M. (2007). A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation. Biochemical Journal, 402(1), 163-173. https://doi.org/10.1042/BJ20060941

A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation. / Lopez, Alex B.; Wang, Chuanping; Huang, Charlie C.; Yaman, Ibrahim; Li, Yi; Chakravarty, Kaushik; Johnson, Peter F.; Chiang, Cheng Ming; Snider, Martin D.; Wek, Ronald C.; Hatzoglou, Maria.

In: Biochemical Journal, Vol. 402, No. 1, 15.02.2007, p. 163-173.

Research output: Contribution to journalArticle

Lopez, AB, Wang, C, Huang, CC, Yaman, I, Li, Y, Chakravarty, K, Johnson, PF, Chiang, CM, Snider, MD, Wek, RC & Hatzoglou, M 2007, 'A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation', Biochemical Journal, vol. 402, no. 1, pp. 163-173. https://doi.org/10.1042/BJ20060941
Lopez, Alex B. ; Wang, Chuanping ; Huang, Charlie C. ; Yaman, Ibrahim ; Li, Yi ; Chakravarty, Kaushik ; Johnson, Peter F. ; Chiang, Cheng Ming ; Snider, Martin D. ; Wek, Ronald C. ; Hatzoglou, Maria. / A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation. In: Biochemical Journal. 2007 ; Vol. 402, No. 1. pp. 163-173.
@article{e80bffa656634004bc52e5b1227dfa66,
title = "A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation",
abstract = "The adaptive response to amino acid limitation in mammalian cells inhibits global protein synthesis and promotes the expression of proteins that protect cells from stress. The arginine/lysine transporter, cat-1, is induced during amino acid starvation by transcriptional and post-transcriptional mechanisms. It is shown in the present study that the transient induction of cat-1 transcription is regulated by the stress response pathway that involves phosphorylation of the translation initiation factor, eIF2 (eukaryotic initiation factor-2). This phosphorylation induces expression of the bZIP (basic leucine zipper protein) transcription factors C/EBP (CCAAT/enhancer-binding protein)-β and ATF (activating transcription factor) 4, which in turn induces ATF3. Transfection experiments in control and mutant cells, and chromatin immunoprecipitations showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1 gene, which functions both in the endogenous and in a heterologous promoter. ATF4 and C/EBPβ activated transcription when expressed in transfected cells and they bound as heterodimers to the AARE in vitro. The induction of transcription by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with C/EBPβ. These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism.",
keywords = "Activating transcription factor, Amino acid response element, Amino acid transporter, eIF2 phosphorylation, Stress response gene, Transcriptional regulation",
author = "Lopez, {Alex B.} and Chuanping Wang and Huang, {Charlie C.} and Ibrahim Yaman and Yi Li and Kaushik Chakravarty and Johnson, {Peter F.} and Chiang, {Cheng Ming} and Snider, {Martin D.} and Wek, {Ronald C.} and Maria Hatzoglou",
year = "2007",
month = "2",
day = "15",
doi = "10.1042/BJ20060941",
language = "English (US)",
volume = "402",
pages = "163--173",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "1",

}

TY - JOUR

T1 - A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation

AU - Lopez, Alex B.

AU - Wang, Chuanping

AU - Huang, Charlie C.

AU - Yaman, Ibrahim

AU - Li, Yi

AU - Chakravarty, Kaushik

AU - Johnson, Peter F.

AU - Chiang, Cheng Ming

AU - Snider, Martin D.

AU - Wek, Ronald C.

AU - Hatzoglou, Maria

PY - 2007/2/15

Y1 - 2007/2/15

N2 - The adaptive response to amino acid limitation in mammalian cells inhibits global protein synthesis and promotes the expression of proteins that protect cells from stress. The arginine/lysine transporter, cat-1, is induced during amino acid starvation by transcriptional and post-transcriptional mechanisms. It is shown in the present study that the transient induction of cat-1 transcription is regulated by the stress response pathway that involves phosphorylation of the translation initiation factor, eIF2 (eukaryotic initiation factor-2). This phosphorylation induces expression of the bZIP (basic leucine zipper protein) transcription factors C/EBP (CCAAT/enhancer-binding protein)-β and ATF (activating transcription factor) 4, which in turn induces ATF3. Transfection experiments in control and mutant cells, and chromatin immunoprecipitations showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1 gene, which functions both in the endogenous and in a heterologous promoter. ATF4 and C/EBPβ activated transcription when expressed in transfected cells and they bound as heterodimers to the AARE in vitro. The induction of transcription by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with C/EBPβ. These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism.

AB - The adaptive response to amino acid limitation in mammalian cells inhibits global protein synthesis and promotes the expression of proteins that protect cells from stress. The arginine/lysine transporter, cat-1, is induced during amino acid starvation by transcriptional and post-transcriptional mechanisms. It is shown in the present study that the transient induction of cat-1 transcription is regulated by the stress response pathway that involves phosphorylation of the translation initiation factor, eIF2 (eukaryotic initiation factor-2). This phosphorylation induces expression of the bZIP (basic leucine zipper protein) transcription factors C/EBP (CCAAT/enhancer-binding protein)-β and ATF (activating transcription factor) 4, which in turn induces ATF3. Transfection experiments in control and mutant cells, and chromatin immunoprecipitations showed that ATF4 activates, whereas ATF3 represses cat-1 transcription, via an AARE (amino acid response element), TGATGAAAC, in the first exon of the cat-1 gene, which functions both in the endogenous and in a heterologous promoter. ATF4 and C/EBPβ activated transcription when expressed in transfected cells and they bound as heterodimers to the AARE in vitro. The induction of transcription by ATF4 was inhibited by ATF3, which also bound to the AARE as a heterodimer with C/EBPβ. These results suggest that the transient increase in cat-1 transcription is due to transcriptional activation caused by ATF4 followed by transcriptional repression by ATF3 via a feedback mechanism.

KW - Activating transcription factor

KW - Amino acid response element

KW - Amino acid transporter

KW - eIF2 phosphorylation

KW - Stress response gene

KW - Transcriptional regulation

UR - http://www.scopus.com/inward/record.url?scp=33847005465&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847005465&partnerID=8YFLogxK

U2 - 10.1042/BJ20060941

DO - 10.1042/BJ20060941

M3 - Article

VL - 402

SP - 163

EP - 173

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 1

ER -