2005/05/04 by Michael S. Kilberg, Yuan‐Xiang Pan, H. Chen +1 · 4 citations
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA modifications and cancer #RNA regulation and disease
paper · doi:10.1146/annurev.nutr.24.012003.132145
openalex publication_date 2005/05/04 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.