title: Bendless modulates JNK-mediated cell death and migration in Drosophila.
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.
authors.affiliation: Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: 1] Department of Interventional Radiology, Shanghai 10th People's Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China [2] Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06519, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xue
authors.affiliation: 1] Howard Hughes Medical Institute, Department of Genetics, Yale University School of Medicine, New Haven, CT 06519, USA [2] Institute of Developmental Biology and Molecular Medicine, Fudan-Yale Center for Biomedical Research, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism; D005260:Female; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D018384:Oxidative Stress / Q000502:physiology; D047992:TNF Receptor-Associated Factor 2 / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D029721:Drosophila Proteins; D047992:TNF Receptor-Associated Factor 2; D044763:Ubiquitin-Conjugating Enzymes; C471544:ben protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases; D020781:Matrix Metalloproteinase 1