ArticleThe Journal of biological chemistry2008
Despite increased ATF4 binding at the C/EBP-ATF composite site following activation of the unfolded protein response, system A transporter 2 (SNAT2) transcription activity is repressed in HepG2 cells.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Brown adipose tissue and skeletal muscle coordinately contribute to thermogenesis in mice.eLife · 2025Article
- miR-10b-5p promotes tumor growth by regulating cell metabolism in liver cancer via targeting SLC38A2.Cancer biology & therapy · 2024Article
- Bacterial over-production of the functionally active human SLC38A2 (SNAT2) exploiting the mistic tag: a cheap and fast tool for testing ligands.Molecular biology reports · 2024Article
- Melatonin Attenuates HInternational journal of molecular sciences · 2022Article
- Regulation of the ATF3 gene by a single promoter in response to amino acid availability and endoplasmic reticulum stress in human primary hepatocytes and hepatoma cells.Biochimica et biophysica acta. Gene regulatory mechanisms · 2018Article
- Surviving Stress: Modulation of ATF4-Mediated Stress Responses in Normal and Malignant Cells.Trends in endocrinology and metabolism: TEM · 2017Review
- Nutritional Stress Induced by Tryptophan-Degrading Enzymes Results in ATF4-Dependent Reprogramming of the Amino Acid Transporter Profile in Tumor Cells.Cancer research · 2016Article
- C/EBPγ Is a Critical Regulator of Cellular Stress Response Networks through Heterodimerization with ATF4.Molecular and cellular biology · 2015Article
- Regulation of glutamine carrier proteins by RNF5 determines breast cancer response to ER stress-inducing chemotherapies.Cancer cell · 2015Article
- Drosophila melanogaster activating transcription factor 4 regulates glycolysis during endoplasmic reticulum stress.G3 (Bethesda, Md.) · 2015Article
- A mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK)-dependent transcriptional program controls activation of the early growth response 1 (EGR1) gene during amino acid limitation.The Journal of biological chemistry · 2014Article
- Expression of a phosphorylated form of ATF4 in lung and non-small cell lung cancer tissues.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Article
- The SLC38 family of sodium-amino acid co-transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Dynamic changes in genomic histone association and modification during activation of the ASNS and ATF3 genes by amino acid limitation.The Biochemical journal · 2013Article
- Heat shock factor 1 is inactivated by amino acid deprivation.Cell stress & chaperones · 2012Article
- ATF4-dependent regulation of the JMJD3 gene during amino acid deprivation can be rescued in Atf4-deficient cells by inhibition of deacetylation.The Journal of biological chemistry · 2012Article
- The transcription factor network associated with the amino acid response in mammalian cells.Advances in nutrition (Bethesda, Md.) · 2012Review
- Functional RNA interference (RNAi) screen identifies system A neutral amino acid transporter 2 (SNAT2) as a mediator of arsenic-induced endoplasmic reticulum stress.The Journal of biological chemistry · 2012Article
- Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise.Journal of applied physiology (Bethesda, Md. : 1985) · 2011Article
- An atypical unfolded protein response in heat shocked cells.PloS one · 2011Article
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Authors and funding
4 authors.
Funding
Abstract
The activated amino acid response (AAR) and unfolded protein response (UPR) stress signaling pathways converge at the phosphorylation of translation initiation factor eIF2alpha. This eIF2alpha modification suppresses global protein synthesis but enhances translation of selected mRNAs such as that for activating transcription factor 4 (ATF4). An ATF4 target gene, SNAT2 (system A sodium-dependent neutral amino acid transporter 2), contains a C/EBP-ATF site that binds ATF4 and triggers increased transcription during the AAR. However, the present studies show that despite increased ATF4 binding to the SNAT2 gene during UPR activation in HepG2 human hepatoma cells, transcription activity was not enhanced. Hyperacetylation of histone H3 and recruitment of the general transcription factors at the HepG2 SNAT2 promoter occurred in response to the AAR but not the UPR. In contrast, the UPR did enhance transcription from a plasmid-based reporter gene driven by a SNAT2 genomic fragment containing the C/EBP-ATF site. Simultaneous activation of the AAR and the UPR pathways revealed that the UPR actually suppressed the increased SNAT2 transcription by the AAR pathway, demonstrating that the UPR pathway generates a repressive signal that acts downstream of ATF4 binding.
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