Affiliation:
1. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Jinan, Shandong 250100, China
Abstract
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 induces FoxO non-phosphorylation and nuclear translocation. Insulin, via Akt, induces FoxO phosphorylation and cytoplasm 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 CarboxypeptidaseA expression for final proteolysis during insect molting. Hence, 20E activates FoxO via upregulating PTEN expression to counteract insulin activity and promote proteolysis.
Funder
This study was supported by the National Natural Science Foundation of China
Publisher
The Company of Biologists
Subject
Developmental Biology,Molecular Biology
Cited by
54 articles.
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