ArticleThe Biochemical journal2007
A feedback transcriptional mechanism controls the level of the arginine/lysine transporter cat-1 during amino acid starvation.
Article in The Biochemical journal, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 89 citations in OpenAlex.
- Soy-dairy protein blend and whey protein ingestion after resistance exercise increases amino acid transport and transporter expression in human skeletal muscle.Journal of applied physiology (Bethesda, Md. : 1985) · 2014Trial
- SOD1 Overexpression Alleviates HAntioxidants (Basel, Switzerland) · 2026Article
- Uterine histotroph and conceptus development. V. Comparative analyses of arginine-mediated transcriptomic reprogramming in conceptus trophectoderm of pigs and sheep†.Biology of reproduction · 2025Article
- Review
- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- Biology of Activating Transcription Factor 4 (ATF4) and Its Role in Skeletal Muscle Atrophy.The Journal of nutrition · 2022Review
- Adaptation to mitochondrial stress requires CHOP-directed tuning of ISR.Science advances · 2021Article
- Proteomics and phosphoproteomics reveal key regulators associated with cytostatic effect of amino acid transporter LAT1 inhibitor.Cancer science · 2021Article
- Targeting the Proline-Glutamine-Asparagine-Arginine Metabolic Axis in Amino Acid Starvation Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The market for amino acids: understanding supply and demand of substrate for more efficient milk protein synthesis.Journal of animal science and biotechnology · 2020Review
- Dual transcriptome analysis reveals differential gene expression modulation influenced byMicrobial genomics · 2020Article
- Activating transcription factor 4 (ATF4) promotes skeletal muscle atrophy by forming a heterodimer with the transcriptional regulator C/EBPβ.The Journal of biological chemistry · 2020Article
- Metabolism of Amino Acids in Cancer.Frontiers in cell and developmental biology · 2020Review
- Metabolic regulation of cell growth and proliferation.Nature reviews. Molecular cell biology · 2019Review
- Regulation of arginine transport by GCN2 eIF2 kinase is important for replication of the intracellular parasite Toxoplasma gondii.PLoS pathogens · 2019Article
- p53 Promotes Cancer Cell Adaptation to Glutamine Deprivation by Upregulating Slc7a3 to Increase Arginine Uptake.Cell reports · 2019Article
- Arginine auxotrophic gene signature in paediatric sarcomas and brain tumours provides a viable target for arginine depletion therapies.Oncotarget · 2017Article
- The gene expression of numerous SLC transporters is altered in the immortalized hypothalamic cell line N25/2 following amino acid starvation.FEBS open bio · 2017Article
- Arginine and Polyamines Fate inFrontiers in microbiology · 2017Review
- GCN2 contributes to mTORC1 inhibition by leucine deprivation through an ATF4 independent mechanism.Scientific reports · 2016Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
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)-beta 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/EBPbeta 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/EBPbeta. 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.