Amino acid response

Amino acid response (AAR) is the mechanism triggered in mammalian cells by amino acid starvation.

The amino acid response pathway is triggered by shortage of any essential amino acid, and results in an increase in activating transcription factor ATF4, which in turn affects many processes by sundry pathways to limit or increase the production of other proteins.^[1]

Proteins increased by AAR

Membrane transporters^[1]
Transcription factors from the basic region/leucine zipper (bZIP) superfamily^[1]^[2]
Growth factors^[1]
Metabolic enzymes ^[1]

Leucine starvation

PCAF is recruited specifically to the CHOP amino acid response element (AARE) to enhance the ATF4 transcriptional activity.^[3]

References

1 2 3 4 5 Kilberg MS, Pan YX, Chen H, Leung-Pineda V. Nutritional control of gene expression: how mammalian cells respond to amino acid limitation*. Annu. Rev. Nutr. 2005;25:59–85.
↑ Chen H, Pan YX, Dudenhausen EE, Kilberg MS. Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation. J. Biol. Chem. 2004;279:50829–50839.
↑ Chérasse Y, Maurin AC, Chaveroux C, et al. (2007). "The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP". Nucleic Acids Res. 35 (17): 5954–65. doi:10.1093/nar/gkm642. PMC 2034469. PMID 17726049.

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[Kilberg-1] 1 2 3 4 5 Kilberg MS, Pan YX, Chen H, Leung-Pineda V. Nutritional control of gene expression: how mammalian cells respond to amino acid limitation*. Annu. Rev. Nutr. 2005;25:59–85.

[Chen_2004-2] Chen H, Pan YX, Dudenhausen EE, Kilberg MS. Amino acid deprivation induces the transcription rate of the human asparagine synthetase gene through a timed program of expression and promoter binding of nutrient-responsive basic region/leucine zipper transcription factors as well as localized histone acetylation. J. Biol. Chem. 2004;279:50829–50839.

[pmid17726049-3] Chérasse Y, Maurin AC, Chaveroux C, et al. (2007). "The p300/CBP-associated factor (PCAF) is a cofactor of ATF4 for amino acid-regulated transcription of CHOP". Nucleic Acids Res. 35 (17): 5954–65. doi:10.1093/nar/gkm642. PMC 2034469. PMID 17726049.