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Screening of suppressors of bax-induced cell death identifies glycerophosphate oxidase-1 as a mediator of debcl-induced apoptosis in Drosophila.

Colin J, Garibal J, Clavier A, Szuplewski S, Risler Y, Milet C, Gaumer S, Guénal I, Mignotte B - Genes Cancer (2015)

Bottom Line: We have previously shown that the mammalian pro-apoptotic Bcl-2 family member Bax is very efficient in inducing apoptosis in Drosophila, allowing the study of bax-induced cell death in a genetic animal model.Most of these suppressors also inhibit debcl-induced phenotypes, suggesting that the activities of both proteins can be modulated in part by common signaling or metabolic pathways.Among these suppressors, Glycerophosphate oxidase-1 is found to participate in debcl-induced apoptosis by increasing mitochondrial reactive oxygen species accumulation.

View Article: PubMed Central - PubMed

Affiliation: Université Versailles St-Quentin, Laboratoire de Génétique et Biologie Cellulaire, Montigny-le-Bretonneux, France ; Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Moléculaire et Physiologique, Montigny-le-Bretonneux, France.

ABSTRACT
Members of the Bcl-2 family are key elements of the apoptotic machinery. In mammals, this multigenic family contains about twenty members, which either promote or inhibit apoptosis. We have previously shown that the mammalian pro-apoptotic Bcl-2 family member Bax is very efficient in inducing apoptosis in Drosophila, allowing the study of bax-induced cell death in a genetic animal model. We report here the results of the screening of a P[UAS]-element insertion library performed to identify gene products that modify the phenotypes induced by the expression of bax in Drosophila melanogaster. We isolated 17 putative modifiers involved in various function or process: the ubiquitin/proteasome pathway; cell growth, proliferation and death; pathfinding and cell adhesion; secretion and extracellular signaling; metabolism and oxidative stress. Most of these suppressors also inhibit debcl-induced phenotypes, suggesting that the activities of both proteins can be modulated in part by common signaling or metabolic pathways. Among these suppressors, Glycerophosphate oxidase-1 is found to participate in debcl-induced apoptosis by increasing mitochondrial reactive oxygen species accumulation.

No MeSH data available.


Related in: MedlinePlus

Examples of modified adult wing phenotypes(A) Wild-type wing. (B-D) Adult wings from bax expressing flies (at 18°C). (B)vg>bax, (C)vg>bax/UY3010, (D)vg>bax ; UY3045.(E-G) Adult wings from debcl expressing flies (at 25°C). (E'-G') are magnifications of (E-G). (E-E')ptc>debcl2(F-F')ptc>debcl2/UY2669, (G-G')ptc>debcl2/UY2111.
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Figure 1: Examples of modified adult wing phenotypes(A) Wild-type wing. (B-D) Adult wings from bax expressing flies (at 18°C). (B)vg>bax, (C)vg>bax/UY3010, (D)vg>bax ; UY3045.(E-G) Adult wings from debcl expressing flies (at 25°C). (E'-G') are magnifications of (E-G). (E-E')ptc>debcl2(F-F')ptc>debcl2/UY2669, (G-G')ptc>debcl2/UY2111.

Mentions: To gain insight into the molecular mechanism of bax-induced apoptosis and with the aim of isolating regulators of this process, we designed a genetic screen for modifiers of Bax-mediated tissue loss in the wing. To ease the screening procedure, we used a strain recombined for vg-GAL4 and UAS-bax transgenes. Animals heterozygous for vg>bax showed a strong and scorable notched wing phenotype (Figure 1B, compared to 1A), facilitating the selection of suppressors rather than enhancers.


Screening of suppressors of bax-induced cell death identifies glycerophosphate oxidase-1 as a mediator of debcl-induced apoptosis in Drosophila.

Colin J, Garibal J, Clavier A, Szuplewski S, Risler Y, Milet C, Gaumer S, Guénal I, Mignotte B - Genes Cancer (2015)

Examples of modified adult wing phenotypes(A) Wild-type wing. (B-D) Adult wings from bax expressing flies (at 18°C). (B)vg>bax, (C)vg>bax/UY3010, (D)vg>bax ; UY3045.(E-G) Adult wings from debcl expressing flies (at 25°C). (E'-G') are magnifications of (E-G). (E-E')ptc>debcl2(F-F')ptc>debcl2/UY2669, (G-G')ptc>debcl2/UY2111.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482245&req=5

Figure 1: Examples of modified adult wing phenotypes(A) Wild-type wing. (B-D) Adult wings from bax expressing flies (at 18°C). (B)vg>bax, (C)vg>bax/UY3010, (D)vg>bax ; UY3045.(E-G) Adult wings from debcl expressing flies (at 25°C). (E'-G') are magnifications of (E-G). (E-E')ptc>debcl2(F-F')ptc>debcl2/UY2669, (G-G')ptc>debcl2/UY2111.
Mentions: To gain insight into the molecular mechanism of bax-induced apoptosis and with the aim of isolating regulators of this process, we designed a genetic screen for modifiers of Bax-mediated tissue loss in the wing. To ease the screening procedure, we used a strain recombined for vg-GAL4 and UAS-bax transgenes. Animals heterozygous for vg>bax showed a strong and scorable notched wing phenotype (Figure 1B, compared to 1A), facilitating the selection of suppressors rather than enhancers.

Bottom Line: We have previously shown that the mammalian pro-apoptotic Bcl-2 family member Bax is very efficient in inducing apoptosis in Drosophila, allowing the study of bax-induced cell death in a genetic animal model.Most of these suppressors also inhibit debcl-induced phenotypes, suggesting that the activities of both proteins can be modulated in part by common signaling or metabolic pathways.Among these suppressors, Glycerophosphate oxidase-1 is found to participate in debcl-induced apoptosis by increasing mitochondrial reactive oxygen species accumulation.

View Article: PubMed Central - PubMed

Affiliation: Université Versailles St-Quentin, Laboratoire de Génétique et Biologie Cellulaire, Montigny-le-Bretonneux, France ; Ecole Pratique des Hautes Etudes, Laboratoire de Génétique Moléculaire et Physiologique, Montigny-le-Bretonneux, France.

ABSTRACT
Members of the Bcl-2 family are key elements of the apoptotic machinery. In mammals, this multigenic family contains about twenty members, which either promote or inhibit apoptosis. We have previously shown that the mammalian pro-apoptotic Bcl-2 family member Bax is very efficient in inducing apoptosis in Drosophila, allowing the study of bax-induced cell death in a genetic animal model. We report here the results of the screening of a P[UAS]-element insertion library performed to identify gene products that modify the phenotypes induced by the expression of bax in Drosophila melanogaster. We isolated 17 putative modifiers involved in various function or process: the ubiquitin/proteasome pathway; cell growth, proliferation and death; pathfinding and cell adhesion; secretion and extracellular signaling; metabolism and oxidative stress. Most of these suppressors also inhibit debcl-induced phenotypes, suggesting that the activities of both proteins can be modulated in part by common signaling or metabolic pathways. Among these suppressors, Glycerophosphate oxidase-1 is found to participate in debcl-induced apoptosis by increasing mitochondrial reactive oxygen species accumulation.

No MeSH data available.


Related in: MedlinePlus