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Molecular data rapidly accumulating on the regulation of gene expression by amino acids in mammalian cells highlight the large variety of mecha-nisms that are involved. Transcription factors, such as the basic-leucine zipper factors, activating transcription factors and CCAAT/enhancer-bind-ing protein, as well as specific regulatory sequences, such as amino acid response element and nutrient-sensing response element, have been shown to mediate the inhibitory effect of some amino acids. | REVIEW ARTICLE Control of mammalian gene expression by amino acids especially glutamine Carole Brasse-Lagnel Alain Lavoinne and Annie Husson AppareilDigestif Environnement et Nutrition EA4311 Université de Rouen France Keywords AARE amino acids ATF gene transcription glutamine mammalian cells NF-kB NSRE signalling pathways transcription factors Correspondence A. Lavoinne Groupe ADEN Faculte de Medecine-Pharmacie de Rouen 22 Boulevard Gambetta Rouen Cedex France Fax 33 2 35 14 82 26 Tel 33 2 35 14 82 40 E-mail Alain.lavoinne@chu-rouen.fr Received 12 November 2008 revised 9 January 2009 accepted 21 January 2009 doi 10.1111 j.1742-4658.2009.06920.x Molecular data rapidly accumulating on the regulation of gene expression by amino acids in mammalian cells highlight the large variety of mechanisms that are involved. Transcription factors such as the basic-leucine zipper factors activating transcription factors and CCAAT enhancer-bind-ing protein as well as specific regulatory sequences such as amino acid response element and nutrient-sensing response element have been shown to mediate the inhibitory effect of some amino acids. Moreover amino acids exert a wide range of effects via the activation of different signalling pathways and various transcription factors and a number of cis elements distinct from amino acid response element nutrient-sensing response element sequences were shown to respond to changes in amino acid concentration. Particular attention has been paid to the effects of glutamine the most abundant amino acid which at appropriate concentrations enhances a great number of cell functions via the activation of various transcription factors. The glutamine-responsive genes and the transcription factors involved correspond tightly to the specific effects of the amino acid in the inflammatory response cell proliferation differentiation and survival and metabolic functions. Indeed in addition to the major role played by nuclear factor-kB in the anti-inflammatory
