title: TRAF6 is a novel regulator of Notch signaling in Drosophila melanogaster.
abstract: Notch signaling pathway unravels a fundamental cellular communication system that plays an elemental role in development. It is evident from different studies that the outcome of Notch signaling depends on signal strength, timing, cell type, and cellular context. Since Notch signaling affects a spectrum of cellular activity at various developmental stages by reorganizing itself in more than one way to produce different intensities in the signaling output, it is important to understand the context dependent complexity of Notch signaling and different routes of its regulation. We identified, TRAF6 (Drosophila homolog of mammalian TRAF6) as an interacting partner of Notch intracellular domain (Notch-ICD). TRAF6 genetically interacts with Notch pathway components in trans-heterozygous combinations. Immunocytochemical analysis shows that TRAF6 co-localizes with Notch in Drosophila third instar larval tissues. Our genetic interaction data suggests that the loss-of-function of TRAF6 leads to the rescue of previously identified Kurtz-Deltex mediated wing notching phenotype and enhances Notch protein survival. Co-expression of TRAF6 and Deltex results in depletion of Notch in the larval wing discs and down-regulates Notch targets, Wingless and Cut. Taken together, our results suggest that TRAF6 may function as a negative regulator of Notch signaling.
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Abhinava K
authors.initials: AK
authors.lastname: Mishra
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Nalani
authors.initials: N
authors.lastname: Sachan
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221 005, India.
authors.forename: Mousumi
authors.initials: M
authors.lastname: Mutsuddi
authors.affiliation: Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi 221 005, India. Electronic address: ashim04@gmail.com.
authors.forename: Ashim
authors.initials: A
authors.lastname: Mukherjee
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D007814:Larva / Q000166:cytology / Q000235:genetics; D010641:Phenotype; D011485:Protein Binding; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000033:anatomy & histology
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D012333:RNA, Messenger; D051880:Receptors, Notch; D048029:TNF Receptor-Associated Factor 6; C586373:TRAF6 protein, Drosophila
keywords: Deltex; Drosophila; Kurtz; Notch; TRAF6