NOPO modulates Egr-induced JNK-independent cell death in Drosophila  

作　　者：Xianjue Ma Jiuhong Huang Lixia Yang Yang Yang Wenzhe Li Lei Xue 

机构地区：[1]Shanghai Key Laboratory for Signaling and Diseases,School of Life Science and Technology,Tongji University,1239 Siping Road,Shanghai 200092,China

出　　处：《Cell Research》2012年第2期425-431,共7页细胞研究（英文版）

基　　金：Acknowledgments We thank Z Wang （Chinese Academy of Sciences）, L Lee （Vanderbilt University, USA）, R Wyman （Yale University, USA）, KBasler （University of Zurich, Switzerland）, M Miura （University of Tokyo, Japan）, T Igaki （Kobe University, Japan）, D Bohmann and H Jasper （University of Rochester, USA）, RK Murphey （Florida Atlantic University, USA）, Bloomington, Harvard, VDRC, Szeged, and NIG stock centers for fly stocks, M Ho （Tongji University, China） and members of Xue lab for discussion and comments. This work is supported by grants from the National Natural Science Foundation of China （30971681 and 31071294）, the National Basic Research Program of China （973 Program; 2010CB944901 and 2011CB943903）, Shanghai Pujiang Program （09PJ1409400）, the Innovation Program of Shanghai Municipal Education Commission （10ZZ27）, Program for New Century Excellent Talents in University （NCET-10-0608） and Shanghai Committee of Science and Technology （09DZ2260100） to L X.

摘　　要：Tumor necrosis factor （TNF） family ligands play essential roles in regulating a variety of cellular processes includ- ing proliferation, differentiation and survival. Expression of Drosophila TNF ortholog Eiger （Egr） induces JNK- dependent cell death, while the roles of caspases in this process remain elusive. To further delineate the Egr-triggered cell death pathway, we performed a genetic screen to identify dominant modifiers of the Egr-induced cell death phenotype. Here we report that Egr elicits a caspase-mediated cell death pathway independent of JNK signaling. Furthermore, we show NOPO, the Drosophila ortholog of TRIP （TRAF interacting protein） encoding an E3 uhiquitin ligase, modulates Egr-induced Caspase-mediated cell death through transcriptional activation of pro-apoptotic genes reaper and hid. Finally, we found Bendless and dUEVla, an ubiquitin-conjugating E2 enzyme complex, regulates NOPO-triggered cell death. Our results indicate that the Ben-dUEVla complex constitutes a molecular switch that bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK and caspases respectively.

关 键 词：cTNF JNK NOPO CASPASE cell death 

分 类 号：Q251[生物学—细胞生物学] Q255