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

M. S. Kilberg, Y. X. Pan, H. Chen, V. Leung-Pineda

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)59-85
Number of pages27
JournalAnnual Review of Nutrition
StatePublished - 2005
Externally publishedYes


  • Metabolite control
  • Nutrient starvation
  • Protein metabolism
  • Transcription
  • mRNA stability

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


Dive into the research topics of 'Nutritional control of gene expression: How mammalian cells respond to amino acid limitation'. Together they form a unique fingerprint.

Cite this