@article {1137726,
	title = {Genome-wide RNAi screening implicates the E3 ubiquitin ligase Sherpa in mediating innate immune signaling by Toll in Drosophila adults},
	journal = {Sci Signal},
	volume = {8},
	year = {2015},
	month = {2015 Oct 27},
	pages = {ra107},
	abstract = {The Drosophila Toll pathway plays important roles in innate immune responses against Gram-positive bacteria and fungi. To identify previously uncharacterized components of this pathway, we performed comparative, ex vivo, genome-wide RNA interference screening. In four screens, we overexpressed the Toll adaptor protein dMyd88, the downstream kinase Pelle, or the nuclear factor κB (NF-κB) homolog Dif, or we knocked down Cactus, the Drosophila homolog of mammalian inhibitor of NF-κB. On the basis of these screens, we identified the E3 ubiquitin ligase Sherpa as being necessary for the activation of Toll signaling. A loss-of-function sherpa mutant fly exhibited compromised production of antimicrobial peptides and enhanced susceptibility to infection by Gram-positive bacteria. In cultured cells, Sherpa mediated ubiquitylation of dMyd88 and Sherpa itself, and Sherpa and Drosophila SUMO (small ubiquitin-like modifier) were required for the proper membrane localization of an adaptor complex containing dMyd88. These findings highlight a role for Sherpa in Drosophila host defense and suggest the SUMOylation-mediated regulation of dMyd88 functions in Toll innate immune signaling.},
	keywords = {Animals, drosophila melanogaster, Drosophila Proteins, Genome-Wide Association Study, Gram-Positive Bacteria, Gram-Positive Bacterial Infections, Protein-Serine-Threonine Kinases, RNA, Small Interfering, SUMO-1 Protein, toll-like receptors, Ubiquitin-Protein Ligases},
	issn = {1937-9145},
	doi = {10.1126/scisignal.2005971},
	author = {Kanoh, Hirotaka and Tong, Li-Li and Kuraishi, Takayuki and Suda, Yamato and Momiuchi, Yoshiki and Shishido, Fumi and Kurata, Shoichiro}
}
