Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
State Key Laboratory of Medical Genomics, Shanghai Institute of Hematology, Department of Hematology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Insect Biochem Mol Biol. 2014 Feb;45:30-9. doi: 10.1016/j.ibmb.2013.11.005. Epub 2013 Dec 4.
During the larval-prepupal transition in Drosophila, a balancing crosstalk occurs between autophagy and caspase activity in the remodeling fat body: the inhibition of autophagy induces caspase activity and the inhibition of caspases induces autophagy. Both autophagy and caspase activity are induced by a pulse of molting hormone (20-hydroxyecdysone, 20E) via the 20E nuclear receptor complex, EcR-USP. We here demonstrate that E93, a 20E primary-response gene encoding an HTH transcription factor, predominantly transduces 20E signaling to induce autophagy and caspase activity in the remodeling fat body. RNAi knockdown or mutation of E93 blocks autophagy and caspase activity, E93 overexpression induces them both, while E93 overexpression has a better rescuing effect on the inhibition of autophagy than caspase activity caused by EcR(DN) overexpression. At the transcriptional level, E93 not only greatly impacts the 20E-triggered transcriptional cascade, but also upregulates essential autophagy and apoptosis genes. Meanwhile, at the phosphorylational level, E93 blocks the PI3K-TORC1 signaling to initiate autophagy. Taken together, we conclude that autophagy and caspase activity are induced by 20E and predominantly transduced by E93 in the remodeling fat body of Drosophila.
在果蝇的幼虫-预蛹转化过程中，自噬和半胱天冬酶活性之间发生平衡串扰，重塑脂肪体：自噬的抑制诱导半胱天冬酶活性，而半胱天冬酶的抑制诱导自噬。自噬和半胱天冬酶活性均由蜕皮激素（20-羟基蜕皮酮，20E）通过 20E 核受体复合物 EcR-USP 诱导产生。我们在此证明，E93（一种编码 HTH 转录因子的 20E 初级反应基因）主要通过 20E 信号转导诱导重塑脂肪体中的自噬和半胱天冬酶活性。E93 的 RNAi 敲低或突变会阻断自噬和半胱天冬酶活性，E93 的过表达会诱导这两种活性，而过表达 E93 对 EcR(DN)过表达引起的自噬抑制的挽救效果要好于对半胱天冬酶活性的抑制。在转录水平上，E93 不仅极大地影响了 20E 触发的转录级联反应，还上调了必需的自噬和凋亡基因。同时，在磷酸化水平上，E93 阻断了 PI3K-TORC1 信号通路以启动自噬。综上所述，我们得出结论，自噬和半胱天冬酶活性是由 20E 诱导的，并且主要由 E93 在果蝇的重塑脂肪体中传递。
