RRC ID 21955
Author Ma X, Huang J, Yang L, Yang Y, Li W, Xue L.
Title NOPO modulates Egr-induced JNK-independent cell death in Drosophila.
Journal Cell Res.
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.
Volume 22(2)
Pages 425-31
Published 2012-2
DOI 10.1038/cr.2011.135
PII cr2011135
PMID 21844890
PMC PMC3271591
MeSH Animals Apoptosis* Caspases / metabolism Drosophila / cytology Drosophila / enzymology Drosophila Proteins / metabolism* JNK Mitogen-Activated Protein Kinases / metabolism* Membrane Proteins / metabolism* Neuropeptides / metabolism Signal Transduction Ubiquitin-Conjugating Enzymes / metabolism Ubiquitin-Protein Ligases / metabolism*
IF 17.848
Times Cited 24