Reference Report

Reference
Citation	Khush, R.S., Cornwell, W.D., Uram, J.N., Lemaitre, B. (2002). A ubiquitin-proteasome pathway represses the Drosophila immune deficiency signaling cascade. Curr. Biol. 12(20): 1728--1737. (Export to RIS)
FlyBase ID	FBrf0151852
Publication Type	Research paper
PubMed ID	12401167
PubMed Abstract	The inducible production of antimicrobial peptides is a major immune response in Drosophila. The genes encoding these peptides are activated by NF-kappaB transcription factors that are controlled by two independent signaling cascades: the Toll pathway that regulates the NF-kappaB homologs, Dorsal and DIF; and the IMD pathway that regulates the compound NF-kappaB-like protein, Relish. Although numerous components of each pathway that are required to induce antimicrobial gene expression have been identified, less is known about the mechanisms that either repress antimicrobial genes in the absence of infection or that downregulate these genes after infection.In a screen for factors that negatively regulate the IMD pathway, we isolated two partial loss-of-function mutations in the SkpA gene that constitutively induce the antibacterial peptide gene, Diptericin, a target of the IMD pathway. These mutations do not affect the systemic expression of the antifungal peptide gene, Drosomycin, a target of the Toll pathway. SkpA encodes a homolog of the yeast and human Skp1 proteins. Skp1 proteins function as subunits of SCF-E3 ubiquitin ligases that target substrates to the 26S proteasome, and mutations affecting either the Drosophila SCF components, Slimb and dCullin1, or the proteasome also induce Diptericin expression. In cultured cells, inhibition of SkpA and Slimb via RNAi increases levels of both the full-length Relish protein and the processed Rel-homology domain.In contrast to other NF-kappaB activation pathways, the Drosophila IMD pathway is repressed by the ubiquitin-proteasome system. A possible target of this proteolytic activity is the Relish transcription factor, suggesting a mechanism for NF-kappaB downregulation in Drosophila.
DOI
Related Publication(s)
Personal communication to FlyBase	dCullin1. Khush, 2003.2.25, dCullin1. [FBrf0157149]
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Curr. Biol.
Title	Current Biology
Publication Year	1991-
ISBN/ISSN	0960-9822
Data from Reference
Aberrations (6)
	Df(1)260-1 Df(1)cin-arth Df(1)sc⁸ Df(1)su(s)83 Df(1)svr Df(1)y74k24.1
Alleles (23)
	Avic\GFP^Drs.PF Avic\GFP^EGFP.Dpt Dredd^B118 imd¹ ird5¹ key¹ lin19^k01207 Prosβ6^1.Scer\UAS Prosβ6¹ Rel^E20 Rel^{Scer\UAS.T:Zzzz\His6} Rel^T:Zzzz\FLAG Scer\GAL4^c564 skpA^+tMa skpA^dsRNA.cKa skpA^G49 skpA^G0109 skpA^G0389 skpA^J6 slmb¹ slmb^dsRNA.cKa Tak1¹ Tl⁸
Constructs (5)
	P{Dpt-GFP.JM863} P{Drs-GFP.JM608} P{skpA.M} P{UAS-DTS5.S} P{UAS-Rel.His6}
Genes (15)
	Avic\GFP Dredd imd ird5 key lin19 Prosβ6 Rel Scer\GAL4 skpA slmb T:Zzzz\FLAG T:Zzzz\His6 Tak1 Tl
Insertions (4)
	P{GawB}c564 P{lacW}lin19^k01207 P{lacW}skpA^G0109 P{lacW}skpA^G0389