title: Amino acid deprivation regulates the stress-inducible gene p8 via the GCN2/ATF4 pathway.
abstract: In mammals, the GCN2/ATF4 pathway has been described as the main pathway involved in the regulation of gene expression upon amino acid limitation. This regulation is notably conferred by the presence of a cis-element called Amino Acid Response Element (AARE) in the promoter of specific genes. In vivo, the notion of amino acid limitation is not limited to nutritional context, indeed several pathological situations are associated with alteration of endogenous amino acid availability. This is notably true in the context of tumour in which the alteration of the microenvironment can lead to a perturbation in nutrient availability. P8 is a small weakly folded multifunctional protein that is overexpressed in several kinds of cancers and whose expression is induced by different stresses. In this study we have demonstrated that amino acid starvation was also able to induce p8 expression. Moreover, we brought the evidence, in vitro and in vivo, that the GCN2/ATF4 pathway is involved in this regulation through the presence of an AARE in p8 promoter.
authors.affiliation: Unité de Nutrition Humaine, UMR1019, INRA de Theix, 63122 Saint-Genès Champanelle, France. julien.averous@clermont.inra.fr
authors.forename: J
authors.initials: J
authors.lastname: Averous
authors.forename: S
authors.initials: S
authors.lastname: Lambert-Langlais
authors.forename: Y
authors.initials: Y
authors.lastname: Cherasse
authors.forename: V
authors.initials: V
authors.lastname: Carraro
authors.forename: L
authors.initials: L
authors.lastname: Parry
authors.forename: W
authors.initials: W
authors.lastname: B'chir
authors.forename: C
authors.initials: C
authors.lastname: Jousse
authors.forename: A C
authors.initials: AC
authors.lastname: Maurin
authors.forename: A
authors.initials: A
authors.lastname: Bruhat
authors.forename: P
authors.initials: P
authors.lastname: Fafournoux
mesh_terms: D051701:Activating Transcription Factor 4 / Q000378:metabolism*; D000596:Amino Acids / Q000172:deficiency*; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D007930:Leucine / Q000172:deficiency; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D050436:Regulatory Elements, Transcriptional
chemical_list: D000596:Amino Acids; C081452:Atf4 protein, mouse; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; C491644:Nupr1 protein, mouse; D051701:Activating Transcription Factor 4; C070634:Eif2ak4 protein, mouse; D017346:Protein Serine-Threonine Kinases; D007930:Leucine