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Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids
Journal article   Open access   Peer reviewed

Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids

Christopher M Adams
The Journal of biological chemistry, Vol.282(23), pp.16744-16753
06/08/2007
DOI: 10.1074/jbc.M610510200
PMID: 17430894
url
https://doi.org/10.1074/jbc.M610510200View
Published (Version of record) Open Access

Abstract

In most mammalian cells, insulin and glucocorticoids promote anabolism and catabolism, respectively. Whereas the opposing effects of insulin and glucocorticoids on catabolic gene expression have been explained at the molecular level, comparatively little is known about how these hormones alter anabolic gene expression. These studies identify ATF4 as an anabolic transcription factor that is repressed by glucocorticoids and induced by insulin. Insulin-mediated induction of ATF4 required the mammalian target of rapamycin complex 1, was required for the activation of a genetic program for the cellular uptake of essential amino acids and the synthesis of nonessential amino acids and aminoacyl-tRNAs, and was coupled to the repression of Foxo-dependent genes needed for protein and lipid catabolism. These results suggest that ATF4 plays a central role in hormonal regulation of amino acid and protein anabolism by coupling amino acid uptake and synthesis, as well as the generation of charged tRNAs, to mammalian target of rapamycin complex 1-mediated mRNA translation.
 Insulin - pharmacology RNA, Messenger - genetics Cells, Cultured Gene Expression Regulation - drug effects Amino Acids - metabolism Anabolic Agents - pharmacology Animals Base Sequence Polymerase Chain Reaction Glucocorticoids - pharmacology Mice RNA, Small Interfering Activating Transcription Factor 4 - physiology

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