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PMID: 16011459 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Nutritional control of gene expression: how mammalian cells respond to amino acid limitation.

Annual review of nutrition ·Vol. 25 ·2005-00-00 ·Pages 59-85

Kilberg MS, Pan YX, Chen H, Leung-Pineda V

Abstract

The amino acid response (AAR) pathway in mammalian cells is designed to detect and respond to amino acid deficiency. Limiting any essential amino acid initiates this signaling cascade, which leads to increased translation of a "master regulator," activating transcription factor (ATF) 4, and ultimately, to regulation of many steps along the pathway of DNA to RNA to protein. These regulated events include chromatin remodeling, RNA splicing, nuclear RNA export, mRNA stabilization, and translational control. Proteins that are increased in their expression as targets of the AAR pathway include membrane transporters, transcription factors from the basic region/leucine zipper (bZIP) superfamily, growth factors, and metabolic enzymes. Significant progress has been achieved in understanding the molecular mechanisms by which amino acids control the synthesis and turnover of mRNA and protein. Beyond gaining additional knowledge of these important regulatory pathways, further characterization of how these processes contribute to the pathology of various disease states represents an interesting aspect of future research in molecular nutrition.

MeSH Terms
Amino Acids/administration & dosage Animals Cell Division Cells/metabolism,ultrastructure Gene Expression Regulation Humans Nutritional Physiological Phenomena/physiology Nutritive Value RNA/biosynthesis,metabolism RNA Splicing RNA, Messenger/metabolism Signal Transduction Transcription Factors
Chemicals
Amino Acids RNA, Messenger Transcription Factors RNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kilberg M S
Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, Florida 32610-0245, USA. mkilberg@ufl.edu
Pan Y-X
Chen H
Leung-Pineda V
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Article Info
Journal
Annual review of nutrition
Abbr.
Annu Rev Nutr
ISSN
0199-9885
DOI
10.1146/annurev.nutr.24.012003.132145
Email
mkilberg@ufl.edu
Published
2005-00-00
Pages
59-85
Language
English
Region
United States
NLM ID
8209988
PMCID
PMC3600373
Subset
IM
Grants
NIDDK NIH HHS · R01 DK052064 · United States
NIDDK NIH HHS · R01 DK059315 · United States
NIDDK NIH HHS · DK-52064 · United States
NIDDK NIH HHS · DK-59315 · United States
External Links
PubMed source DOI: 10.1146/annurev.nutr.24.012003.132145 PMC Full Text View journal details
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