Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids
Role of the transcription factor ATF4 in the anabolic actions of insulin and the anti-anabolic actions of glucocorticoids
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DOI：
10.1074/jbc.m610510200
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发表时间：
2007-06-08
影响因子：
4.8
通讯作者：
Adams, Christopher M.
中科院分区：
文献类型：
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作者：
Adams, Christopher M.
在大多数哺乳动物细胞中，胰岛素和糖皮质激素分别促进合成代谢和分解代谢。虽然胰岛素和糖皮质激素对分解代谢基因表达的相反作用已经在分子水平上得到了解释，但相对而言，人们对这些激素如何改变合成代谢基因表达知之甚少。这些研究表明ATF4是一种糖皮质激素抑制和胰岛素诱导的合成代谢转录因子。胰岛素介导的ATF4诱导需要雷帕霉素复合物1的哺乳动物靶点，是激活细胞摄取必需氨基酸和合成非必需氨基酸和氨基酰基trna的遗传程序所必需的，并且与抑制蛋白质和脂质分解代谢所需的foxo依赖基因相结合。这些结果表明，ATF4通过将氨基酸摄取和合成以及带电trna的产生偶联到哺乳动物雷帕霉素复合物1介导的mRNA翻译靶点，在氨基酸和蛋白质合成代谢的激素调节中起核心作用。
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.