Document Detail


Amino acid limitation regulates the expression of genes involved in several specific biological processes through GCN2-dependent and GCN2-independent pathways.
MedLine Citation:
PMID:  19120448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Evidence has accumulated that amino acids play an important role in controlling gene expression. Nevertheless, two components of the amino acid control of gene expression are not yet completely understood in mammals: (a) the target genes and biological processes regulated by amino acid availability, and (b) the signaling pathways that mediate the amino acid response. Using large-scale analysis of gene expression, the objective of this study was to gain a better understanding of the control of gene expression by amino acid limitation. We found that a 6 h period of leucine starvation regulated the expression of a specific set of genes: 420 genes were up-regulated by more than 1.8-fold and 311 genes were down-regulated. These genes were involved in the control of several biological processes, such as amino acid metabolism, lipid metabolism and signal regulation. Using GCN2-/- cells and rapamycin treatment, we checked for the role of mGCN2 and mTORC1 kinases in this regulation. We found that (a) the GCN2 pathway was the major, but not unique, signaling pathway involved in the up- and down-regulation of gene expression in response to amino acid starvation, and (b) that rapamycin regulates the expression of a set of genes that only partially overlaps with the set of genes regulated by leucine starvation.
Authors:
Christiane Deval; Cédric Chaveroux; Anne-Catherine Maurin; Yoan Cherasse; Laurent Parry; Valérie Carraro; Dragan Milenkovic; Marc Ferrara; Alain Bruhat; Céline Jousse; Pierre Fafournoux
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Publication Detail:
Type:  Journal Article     Date:  2008-12-19
Journal Detail:
Title:  The FEBS journal     Volume:  276     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-15     Completed Date:  2009-02-10     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  707-18     Citation Subset:  IM    
Affiliation:
Unité de Nutrition Humaine, Equipe Génes-Nutriments, Saint Genès Champanelle, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism*
Animals
Cell Line
Gene Expression Regulation / drug effects,  genetics*
Mice
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Protein Processing, Post-Translational
Protein-Serine-Threonine Kinases / deficiency,  genetics,  metabolism*
RNA, Messenger / genetics
Signal Transduction*
Sirolimus / pharmacology
Transcription, Genetic / genetics
Chemical
Reg. No./Substance:
0/Amino Acids; 0/RNA, Messenger; 53123-88-9/Sirolimus; EC 2.7.11.1/Eif2ak4 protein, mouse; EC 2.7.11.1/Protein-Serine-Threonine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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