Apoptosis Database

Description [+]

Synonyms: BG4, DEATH DOMAIN-CONTAINING ADAPTER PROTEIN BG4, FAS-ASSOCIATED DEATH DOMAIN-CONTAINING PROTEIN
Species: Metazoa;Bilateria;Ecdysozoa;Arthropoda;Hexapoda; Drosophila melanogaster
Short gene description: NA
Family: Death Domain-containing protein : DD adapter protein
Process: immunity,
Pathways: TNF/NF-kappaB signaling,
Criteria: manually curated
Curator comment:
WIKI: BG4-D_melanogaster

References [+]

dFADD, a novel death domain-containing adapter protein for the Drosophila caspase DREDD.
Hu S, Yang X
Apoptotic cell death occurs through activation of procaspases, the precursors of a group of aspartate-specific cysteine proteases known as caspases. Procaspase activation is mediated by death adapter proteins such as the mammalian proteins FADD and Apaf-1 and the Caenorhabditis elegans protein CED-4. These adapters bind to procaspases and facilitate oligomerization and subsequent auto-proteolytic processing of the zymogens. Here we report cloning and characterization of dFADD, a FADD homologue in Drosophila. dFADD contains a death domain that is highly homologous to the FADD death domain, and it also shares a novel domain with a Drosophila caspase DREDD, which we call death-inducing domain. dFADD binds to DREDD through the death-inducing domain and enhances the cell death activity and proteolytic processing of DREDD. dFADD and DREDD are stabilized by their interaction. The structural and functional similarities between dFADD and FADD suggest the existence of a FADD-like apoptosis pathway in Drosophila. J Biol Chem. 2000 Oct 6;275(40):30761-4.

The Drosophila immune defense against gram-negative infection requires the death protein dFADD.
Naitza S, Rosse C, Kappler C, Georgel P, Belvin M, Gubb D, Camonis J, Hoffmann JA, Reichhart JM
Drosophila responds to Gram-negative infections by mounting an immune response that depends on components of the IMD pathway. We recently showed that imd encodes a protein with a death domain with high similarity to that of mammalian RIP. Using a two-hybrid screen in yeast, we have isolated the death protein dFADD as a molecule that associates with IMD. Our data show that loss of dFADD function renders flies highly susceptible to Gram-negative infections without affecting resistance to Gram-positive bacteria. By genetic analysis we show that dFADD acts downstream of IMD in the pathway that controls inducibility of the antibacterial peptide genes. Immunity. 2002 Nov;17(5):575-81.

Inducible expression of double-stranded RNA reveals a role for dFADD in the regulation of the antibacterial response in Drosophila adults.
Leulier F, Vidal S, Saigo K, Ueda R, Lemaitre B
In Drosophila, the immune deficiency (Imd) pathway controls antibacterial peptide gene expression in the fat body in response to Gram-negative bacterial infection. The ultimate target of the Imd pathway is Relish, a transactivator related to mammalian P105 and P100 NF-kappaB precursors. Relish is processed in order to translocate to the nucleus, and this cleavage is dependent on both Dredd, an apical caspase related to caspase-8 of mammals, and the fly Ikappa-B kinase complex (dmIKK). dTAK1, a MAPKKK, functions upstream of the dmIKK complex and downstream of Imd, a protein with a death domain similar to that of mammalian receptor interacting protein (RIP). Finally, the peptidoglycan recognition protein-LC (PGRP-LC) acts upstream of Imd and probably functions as a receptor for the Imd pathway. Using inducible expression of dFADD double-stranded RNA, we demonstrate that dFADD is a novel component of the Imd pathway: dFADD double-stranded RNA expression reduces the induction of antibacterial peptide-encoding genes after infection and renders the fly susceptible to Gram-negative bacterial infection. Epistatic studies indicate that dFADD acts between Imd and Dredd. Our results reinforce the parallels between the Imd and the TNF-R1 pathways. Curr Biol. 2002 Jun 25;12(12):996-1000.

Structure & Sequence [+]

Source	Domain Name	Start	End
PFAM A	Death	152	237

Evolution [+]

Information from other databases [+]

Gene related links:

Protein related links:

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BG4 (Drosophila melanogaster)