Abstract
The TNF–JNK pathway is a highly conserved signaling pathway that regulates a wide spectrum of biological processes including cell death and migration. To further delineate this pathway, we carried out a genetic screen for dominant modifiers of the cell death phenotype triggered by ectopic expression of Eiger (Egr), the Drosophila TNF ortholog. Here we show that Bendless (Ben), an E2 ubiquitin-conjugating enzyme, modulates Egr-induced JNK activation and cell death through dTRAF2. Furthermore, Ben physically interacts with dTRAF2 and regulates Egr-induced dTRAF2 polyubiquitination. Finally, Ben is required for JNK-dependent tumor progression, cell migration, oxidative stress resistance and longevity. Our results indicate that Ben constitutes an essential component of the evolutionarily conserved TNF–JNK pathway that modulates cell death and invasion, tumor progression, stress response and lifespan in metazoans.
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Abbreviations
- TNF:
-
tumor necrosis factor
- JNK:
-
c-Jun N-terminal Kinase
- MAPK:
-
mitogen-activated protein kinases
- GMR:
-
glass multiple reporter
- MF:
-
morphogenetic furrow
- MARCM:
-
mosaic analysis with a repressible cell marker
- ey:
-
eyeless
- VNC:
-
ventral nerve cord
- MMP1:
-
matrix metalloproteinase 1
- A/P:
-
anterior/posterior
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Acknowledgements
We thank R Wyman, M Tanouye, J Chung, M Miura, K Basler, D Bohmann, Bloomington, Harvard, VDRC and NIG stock centers for fly stocks, A Srivastava for technical assistance and M Ho for discussion and comments. This work was supported by the National Basic Research Program of China (973 Program) (grant no. 2010CB944901 and 2011CB943903), National Natural Science Foundation of China (grant no. 31071294, 31171413 and 31371490), the PhD Programs Foundation of Ministry of Education of China (grant no. 20120072120030 and 20120072110023) and Shanghai Committee of Science and Technology (grant no. 09DZ2260100) to LX, the National Institutes of Health grant to TX. TX is an investigator of the Howard Hughes Medical Institute.
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Ma, X., Li, W., Yu, H. et al. Bendless modulates JNK-mediated cell death and migration in Drosophila. Cell Death Differ 21, 407–415 (2014). https://doi.org/10.1038/cdd.2013.154
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DOI: https://doi.org/10.1038/cdd.2013.154
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