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.

journal_name

Cell Res

journal_title

Cell research

authors

Ma X,Huang J,Yang L,Yang Y,Li W,Xue L

doi

10.1038/cr.2011.135

subject

Has Abstract

pub_date

2012-02-01 00:00:00

pages

425-31

issue

2

eissn

1001-0602

issn

1748-7838

pii

cr2011135

journal_volume

22

pub_type

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