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Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery.

Colussi PA, Quinn LM, Huang DC, Coombe M, Read SH, Richardson H, Kumar S - J. Cell Biol. (2000)

Bottom Line: Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects.RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos.These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

View Article: PubMed Central - PubMed

Affiliation: The Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia.

ABSTRACT
Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

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Possible position of Debcl in the Drosophila cell death pathway leading to caspase activation. Several genetic and biochemical studies have established the possible hierarchy between various components of the Drosophila cell death machinery (reviewed in Abrams 1999). The studies described in this paper place Debcl upstream of the P35-inhibitable, Dark-mediated caspase activation pathway. Debcl may lie downstream of the proteins of the H99 complex (Reaper, Grim, and Hid). However, further experiments are required to firmly place Debcl and H99 in the same genetic pathway. Similar to mammalian death pathways, Debcl may function by antagonizing a yet undiscovered prosurvival Bcl-2–like protein(s) (shown as DsBcl-2) in Drosophila.
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Figure 9: Possible position of Debcl in the Drosophila cell death pathway leading to caspase activation. Several genetic and biochemical studies have established the possible hierarchy between various components of the Drosophila cell death machinery (reviewed in Abrams 1999). The studies described in this paper place Debcl upstream of the P35-inhibitable, Dark-mediated caspase activation pathway. Debcl may lie downstream of the proteins of the H99 complex (Reaper, Grim, and Hid). However, further experiments are required to firmly place Debcl and H99 in the same genetic pathway. Similar to mammalian death pathways, Debcl may function by antagonizing a yet undiscovered prosurvival Bcl-2–like protein(s) (shown as DsBcl-2) in Drosophila.

Mentions: Although debcl expression is low during embryonic and larval development, the expression appears to correlate with cell death in various tissues. With the exception of early embryos, our TUNEL data suggest that debcl may be expressed mainly in the cells that are destined to die. The function of higher debcl mRNA levels in early embryos is currently not known. Transgenic experiments show that ectopic Debcl expression is accompanied by potent apoptosis induction. This may explain why debcl expression is mostly limited to cells that are committed to undergo programed cell death during development. The closest mammalian relative of Debcl, Bok, is mainly expressed in adult reproductive tissues (Hsu et al. 1997). In adult female flies, debcl expression is relatively high and may be mainly contributed by the ovaries. Thus, debcl may function throughout embryonic and larval development, and also in the apoptosis of nurse cells in the adult ovaries. Our in vitro and in vivo data with P35 clearly shows that debcl-induced cell death is caspase-dependent and that Debcl lies upstream of caspases in the death pathway. Additionally, an inhibition of debcl eye phenotype in dark mutant flies further substantiates the finding that Debcl lies upstream of the Dark-mediated caspase activation pathway (Fig. 9). Given that debcl RNAi suppresses most of the programed cell death in embryos, debcl is likely to be a critical regulator of cell death during embryogenesis. Since embryos injected with the debcl double-stranded RNA do not progress into larval development, it was not possible to study the function of debcl later in development using RNAi technique.


Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery.

Colussi PA, Quinn LM, Huang DC, Coombe M, Read SH, Richardson H, Kumar S - J. Cell Biol. (2000)

Possible position of Debcl in the Drosophila cell death pathway leading to caspase activation. Several genetic and biochemical studies have established the possible hierarchy between various components of the Drosophila cell death machinery (reviewed in Abrams 1999). The studies described in this paper place Debcl upstream of the P35-inhibitable, Dark-mediated caspase activation pathway. Debcl may lie downstream of the proteins of the H99 complex (Reaper, Grim, and Hid). However, further experiments are required to firmly place Debcl and H99 in the same genetic pathway. Similar to mammalian death pathways, Debcl may function by antagonizing a yet undiscovered prosurvival Bcl-2–like protein(s) (shown as DsBcl-2) in Drosophila.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2169366&req=5

Figure 9: Possible position of Debcl in the Drosophila cell death pathway leading to caspase activation. Several genetic and biochemical studies have established the possible hierarchy between various components of the Drosophila cell death machinery (reviewed in Abrams 1999). The studies described in this paper place Debcl upstream of the P35-inhibitable, Dark-mediated caspase activation pathway. Debcl may lie downstream of the proteins of the H99 complex (Reaper, Grim, and Hid). However, further experiments are required to firmly place Debcl and H99 in the same genetic pathway. Similar to mammalian death pathways, Debcl may function by antagonizing a yet undiscovered prosurvival Bcl-2–like protein(s) (shown as DsBcl-2) in Drosophila.
Mentions: Although debcl expression is low during embryonic and larval development, the expression appears to correlate with cell death in various tissues. With the exception of early embryos, our TUNEL data suggest that debcl may be expressed mainly in the cells that are destined to die. The function of higher debcl mRNA levels in early embryos is currently not known. Transgenic experiments show that ectopic Debcl expression is accompanied by potent apoptosis induction. This may explain why debcl expression is mostly limited to cells that are committed to undergo programed cell death during development. The closest mammalian relative of Debcl, Bok, is mainly expressed in adult reproductive tissues (Hsu et al. 1997). In adult female flies, debcl expression is relatively high and may be mainly contributed by the ovaries. Thus, debcl may function throughout embryonic and larval development, and also in the apoptosis of nurse cells in the adult ovaries. Our in vitro and in vivo data with P35 clearly shows that debcl-induced cell death is caspase-dependent and that Debcl lies upstream of caspases in the death pathway. Additionally, an inhibition of debcl eye phenotype in dark mutant flies further substantiates the finding that Debcl lies upstream of the Dark-mediated caspase activation pathway (Fig. 9). Given that debcl RNAi suppresses most of the programed cell death in embryos, debcl is likely to be a critical regulator of cell death during embryogenesis. Since embryos injected with the debcl double-stranded RNA do not progress into larval development, it was not possible to study the function of debcl later in development using RNAi technique.

Bottom Line: Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects.RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos.These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

View Article: PubMed Central - PubMed

Affiliation: The Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia.

ABSTRACT
Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

Show MeSH
Related in: MedlinePlus