Reference Report

Reference
Citation	Wing, J.P., Schreader, B.A., Yokokura, T., Wang, Y., Andrews, P.S., Huseinovic, N., Dong, C.K., Ogdahl, J.L., Schwartz, L.M., White, K., Nambu, J.R. (2002). Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis. Nat. Cell Biol. 4(6): 451--456. (Export to RIS)
FlyBase ID	FBrf0149135
Publication Type	Research paper
PubMed ID	12021772
PubMed Abstract	In Drosophila melanogaster, apoptosis is controlled by the integrated actions of the Grim-Reaper (Grim-Rpr) and Drosophila Inhibitor of Apoptosis (DIAP) proteins (reviewed in refs 1 4). The anti-apoptotic DIAPs bind to caspases and inhibit their proteolytic activities. DIAPs also bind to Grim-Rpr proteins, an interaction that promotes caspase activity and the initiation of apoptosis. Using a genetic modifier screen, we identified four enhancers of grim-reaper-induced apoptosis that all regulate ubiquitination processes: uba-1, skpA, fat facets (faf), and morgue. Strikingly, morgue encodes a unique protein that contains both an F box and a ubiquitin E2 conjugase domain that lacks the active site Cys required for ubiquitin linkage. A reduction of morgue activity suppressed grim-reaper-induced cell death in Drosophila. In cultured cells, Morgue induced apoptosis that was suppressed by DIAP1. Targeted morgue expression downregulated DIAP1 levels in Drosophila tissue, and Morgue and Rpr together downregulated DIAP1 levels in cultured cells. Consistent with potential substrate binding functions in an SCF ubiquitin E3 ligase complex, Morgue exhibited F box-dependent association with SkpA and F box-independent association with DIAP1. Morgue may thus have a key function in apoptosis by targeting DIAP1 for ubiquitination and turnover.
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Nat. Cell Biol.
Title	Nature Cell Biology
Publication Year	1999-
ISBN/ISSN	1465-7392 1476-4679
Data from Reference
Aberrations (2)
	Df(2L)dp-h25 Df(2L)morgue¹⁹
Alleles (20)
	CG15432¹⁹ Ecol\lacZ^Scer\UAS.cUa EP1216b^EP1216b faf^EP3520 grim::rpr^rg.Scer\UAS grim^Scer\UAS.cNa morgue¹⁹ morgue^cWa morgue^EP1184 morgue^EP2367 rpr^GMR.PW rpr^MtnA.PK rpr^Scer\UAS.cZa Scer\GAL4^GMR.PF Scer\GAL4^Gp150-52A skpA^EP1216a skpA^EP1423 th^MtnA.PW Uba1^EP2375 W^GMR.PG
Constructs (7)
	P{GAL4-ninaE.GMR} P{GMR-hid} P{GMR-rpr.W} P{UAS-grim.N} P{UAS-lacZ.U} P{UAS-r/grim} P{UAS-rpr.Z}
Genes (16)
	CG15432 Ecol\lacZ eff Elp3 EP1216b faf grim grim::rpr morgue rpr Scer\GAL4 skl skpA th Uba1 W
Insertions (8)
	P{EP}EP1216b^EP1216b P{EP}faf^EP3520 P{EP}Hmt4-20^EP1216a P{EP}morgue^EP1184 P{EP}morgue^EP2367 P{EP}skpA^EP1423 P{EP}Uba1^EP2375 P{GawB}Gp150^52A