4E-BP functions as a metabolic brake used under stress conditions but not during normal growth
4E-BP functions as a metabolic brake used under stress conditions but not during normal growth
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DOI：
10.1101/gad.341505
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发表时间：
2005-08-15
影响因子：
10.5
通讯作者：
Cohen, SM
中科院分区：
文献类型：
--
作者：
Teleman, AA;Chen, YW;Cohen, SM
4E-BP 是细胞内整体翻译水平的重要调节因子。通过结合 eIF4E，4E-BP 会损害 40S 核糖体亚基向所有真核细胞 mRNA 5' 端存在的帽子结构的募集。 4E-BP 活性由 TOR（雷帕霉素靶标）控制。 4E-BP 已在细胞培养中得到广泛研究；然而，4E-BP 在生物体发育中的生物学作用迄今为止尚不清楚。由于 TOR 已被证明可以控制动物发育过程中的组织生长，因此 4E-BP 也被认为可以充当生长调节剂。在这里，我们研究了 4E-BP 功能与有机体发育的相关性，并为另一种观点提供了证据。我们发现 4E-BP 强烈影响果蝇的脂肪代谢。我们建议 4E-BP 作为代谢制动器，在环境压力条件下被激活，以控制脂肪代谢。 4E-BP突变体缺乏这种调节，降低了它们在不利条件下生存的能力。
4E-BP is an important regulator of overall translation levels in cells. By binding eIF4E, 4E-BP impairs recruitment of the 40S ribosomal subunit to the cap structure present at the 5'-end of all eukaryotic cellular mRNAs. 4E-BP activity is controlled by TOR (Target of Rapamycin). 4E-BP has been studied extensively in cell culture; however, the biological role of 4E-BP in developing organisms is unclear to date. Since TOR has been shown to control tissue growth during animal development, 4E-BP has also been assumed to serve as a growth regulator. Here, we study the relevance of 4E-BP function for organismal development, and present evidence for an alternate view. We show that 4E-BP strongly affects fat metabolism in Drosophila. We suggest that 4E-BP works as a metabolic brake that is activated under conditions of environmental stress to control fat metabolism. 4E-BP mutants lack this regulation, reducing their ability to survive under unfavorable conditions.