reaper and bax initiate two different apoptotic pathways affecting mitochondria and antagonized by bcl-2 in Drosophila.
bcl-2 was the first regulator of apoptosis shown to be involved in oncogenesis. Subsequent studies in mammals, in the nematode and in Drosophila revealed wide evolutionary conservation of the regulation of apoptosis. Although dbok/debcl, a member of the bcl-2 gene family described in Drosophila, shows pro-apoptotic activities, no anti-apoptotic bcl-2 family gene has been studied in Drosophila. We have previously reported that the human anti-apoptotic gene bcl-2 is functional in Drosophila, suggesting that the fruit fly shares regulatory mechanisms with vertebrates and the nematode, involving anti-apoptotic members of the bcl-2 family. We now report that bcl-2 suppresses rpr-induced apoptosis in Drosophila. Additionally, we have compared features of bax- and rpr-induced apoptosis. Flow cytometry analysis of wing disc cells demonstrate that both killers trigger mitochondrial defects. Interestingly, bcl-2 suppresses both bax- and rpr-induced mitochondrial defects while the caspase-inhibitor p35 is specific to the rpr pathway. Finally, we show that the inhibition of apoptosis by bcl-2 is associated with the down-regulation of rpr expression.
Brun
Sylvain
S
Laboratoire de Génétique et Biologie Cellulaire, CNRS UPRES-A 8087, et Laboratoire de Génétique Moléculaire et Physiologie de l'EPHE, Université de Versailles-St Quentin en Yvelines, 45 avenue des Etats-Unis, F-78035 Versailles cedex, France.
Rincheval
Vincent
V
Gaumer
Sébastien
S
Mignotte
Bernard
B
Guenal
Isabelle
I
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism / Q000494:pharmacology; D003433:Crosses, Genetic; D015536:Down-Regulation; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D005434:Flow Cytometry; D007763:Lac Operon / Q000502:physiology; D008074:Lipoproteins / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D008928:Mitochondria / Q000502:physiology*; D010455:Peptides / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism* / Q000494:pharmacology; D014764:Viral Proteins; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism*; D051028:bcl-2-Associated X Protein; D001616:beta-Galactosidase / Q000378:metabolism
D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D029721:Drosophila Proteins; D008074:Lipoproteins; D010455:Peptides; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein; C492234:p35 protein, Baculovirus; C086973:rpr protein, Drosophila; D001616:beta-Galactosidase