机构：[1]The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China[2]International Academy of Targeted Therapeutics and Innovation, Chongqing University of Arts and Sciences, Chongqing, China[3]Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Objectives The evolutionary conserved JNK pathway plays crucial role in cell death, yet factors that modulate this signalling have not been fully disclosed. In this study, we aim to identify additional factors that regulate JNK signalling in cell death, and characterize the underlying mechanisms. Materials and Methods Drosophila were raised on standard media, and cross was carried out at 25 degrees C. The Gal4/UAS system was used to express proteins or RNAi in a specific temporal and spatial pattern. Gene expression was revealed by GFP fluorescence, X-gal staining or immunostaining of 3rd instar larval eye and wing discs. Cell death was visualized by acridine orange (AO) staining. Images of fly eyes and wings were taken by OLYMPUS microscopes. Results We found that licorne (lic) encoding the Drosophila MKK3 is an essential regulator of JNK-mediated cell death. Firstly, loss of lic suppressed ectopic Egr-triggered JNK activation and cell death in eye and wing development. Secondary, lic is necessary for loss-of-cell polarity-induced, physiological JNK-dependent cell death in wing development. Thirdly, Lic overexpression is sufficient to initiate JNK-mediated cell death in developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that Lic acts in parallel with Hep in the Egr-JNK pathway. Conclusions This study not only identified Lic as a novel component of the JNK signalling, but also disclosed the crucial roles and mechanism of Lic in cell death.
基金：
National Natural Science Foundation of
China, Grant/Award Number: 31571516
and 31771595; Shanghai Committee of
Science and Technology, Grant/Award
Number: 09DZ2260100, 18140900400 and
18430711600
第一作者机构：[1]The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China
通讯作者：
通讯机构：[1]The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China[*1]The First Rehabilitation Hospital of Shanghai, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, Shanghai, China.
推荐引用方式(GB/T 7714)：
Sun Yihao,Zhang Di,Li Chenglin,et al.Lic regulates JNK-mediated cell death in Drosophila[J].CELL PROLIFERATION.2019,52(3):doi:10.1111/cpr.12593.
APA：
Sun, Yihao,Zhang, Di,Li, Chenglin,Huang, Jiuhong,Li, Wenzhe...&Xue, Lei.(2019).Lic regulates JNK-mediated cell death in Drosophila.CELL PROLIFERATION,52,(3)
MLA：
Sun, Yihao,et al."Lic regulates JNK-mediated cell death in Drosophila".CELL PROLIFERATION 52..3(2019)
生物学