title: NOPO modulates Egr-induced JNK-independent cell death in Drosophila.
abstract: Tumor necrosis factor (TNF) family ligands play essential roles in regulating a variety of cellular processes including 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 ubiquitin ligase, modulates Egr-induced Caspase-mediated cell death through transcriptional activation of pro-apoptotic genes reaper and hid. Finally, we found Bendless and dUEV1a, an ubiquitin-conjugating E2 enzyme complex, regulates NOPO-triggered cell death. Our results indicate that the Ben-dUEV1a complex constitutes a molecular switch that bifurcates the Egr-induced cell death signaling into two pathways mediated by JNK and caspases respectively.
authors.affiliation: Shanghai Key Laboratory for Signaling and Diseases, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Xianjue
authors.initials: X
authors.lastname: Ma
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Huang
authors.forename: Lixia
authors.initials: L
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004330:Drosophila / Q000166:cytology / Q000201:enzymology; D029721:Drosophila Proteins / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D015398:Signal Transduction; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D008565:Membrane Proteins; D009479:Neuropeptides; C464573:egr protein, Drosophila; C086973:rpr protein, Drosophila; D044763:Ubiquitin-Conjugating Enzymes; C471544:ben protein, Drosophila; C540453:NOPO protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D048031:JNK Mitogen-Activated Protein Kinases; D020169:Caspases