20-hydroxyecdysone activates Forkhead box O to promote proteolysis during Helicoverpa armigera molting
20-hydroxyecdysone activates Forkhead box O to promote proteolysis during Helicoverpa armigera molting
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20-羟基蜕皮酮激活叉头盒 O 促进棉铃虫蜕皮过程中的蛋白水解
DOI：
10.1242/dev.128694
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发表时间：
2016-03-15
期刊：
影响因子：
4.6
通讯作者：
Zhao, Xiao-Fan
中科院分区：
文献类型：
--
作者：
Cai, Mei-Juan;Zhao, Wen-Li;Zhao, Xiao-Fan
胰岛素抑制转录因子叉头框O（FoxO）的活性，而类固醇激素20 - 羟基蜕皮酮（20E）激活FoxO；然而，其机制尚不清楚。我们假设20E上调磷脂酰肌醇 - 3,4,5 - 三磷酸3 - 磷酸酶（PTEN）的表达以激活FoxO，从而促进鳞翅目昆虫棉铃虫蜕皮过程中的蛋白质水解。FoxO的表达在蜕皮和变态过程中增加。在五龄幼虫中敲低FoxO会导致幼虫蜕皮失败。20E抑制FoxO的磷酸化，导致FoxO核转位。胰岛素通过Akt诱导FoxO磷酸化和细胞质定位。20E抑制胰岛素诱导的Akt磷酸化和FoxO磷酸化。20E通过蜕皮激素受体B1（EcRB1）和超气门蛋白（USP1）上调PTEN的表达，PTEN抑制Akt磷酸化，从而抑制FoxO磷酸化。未磷酸化的FoxO进入细胞核并附着在Broad异构体7（BrZ7）基因上游区域的FoxO结合元件上，在20E诱导下调节BrZ7的转录。20E通过EcRB1和USP1上调FoxO的表达。FoxO对BrZ7表达的调节可调节羧肽酶A的表达，以促进昆虫蜕皮过程中的最终蛋白质水解。因此，20E通过上调PTEN的表达激活FoxO，以抵消胰岛素的活性并促进蛋白质水解。
Insulin inhibits transcription factor Forkhead box O (FoxO) activity, and the steroid hormone 20-hydroxyecdysone (20E) activates FoxO; however, the mechanism is unclear. We hypothesized that 20E upregulates phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN) expression to activate FoxO, thereby promoting proteolysis during molting in the lepidopteran insect Helicoverpa armigera. FoxO expression is increased during molting and metamorphosis. The knockdown of FoxO in fifth instar larvae results in larval molting failure. 20E inhibits FoxO phosphorylation, resulting in FoxO nuclear translocation. Insulin, via Akt, induces FoxO phosphorylation and cytoplasmic localization. 20E represses insulin-induced Akt phosphorylation and FoxO phosphorylation. 20E, via ecdysone receptor B1 (EcRB1) and the ultraspiracle protein (USP1), upregulates PTEN expression, which represses Akt phosphorylation, thereby repressing FoxO phosphorylation. The non-phosphorylated FoxO enters the nucleus and attaches to a FoxO-binding element in the upstream region of the Broad isoform 7 (BrZ7) gene to regulate BrZ7 transcription under 20E induction. 20E upregulates FoxO expression via EcRB1 and USP1. FoxO regulation of BrZ7 expression regulates Carboxypeptidase A expression for final proteolysis during insect molting. Hence, 20E activates FoxO via upregulating PTEN expression to counteract insulin activity and promote proteolysis. Summary: Steroid hormone 20E upregulates PTEN expression to inhibit insulin-induced Akt and FoxO phosphorylation, resulting in non-phosphorylated FoxO nuclear localisation.