title: Drosophila pro-apoptotic Bcl-2/Bax homologue reveals evolutionary conservation of cell death mechanisms.
abstract: Genetic analysis of programmed cell death in Drosophila reveals many similarities with mammals. Heretofore, a missing link in the fly has been the absence of any Bcl-2/Bax family members, proteins that function in mammals as regulators of mitochondrial cytochrome c release. A Drosophila homologue of the human killer protein Bok (DBok) was identified. The predicted structure of DBok is similar to pore-forming Bcl-2/Bax family members. DBok induces apoptosis in insect and human cells, which is suppressible by anti-apoptotic human Bcl-2 family proteins. A caspase inhibitor suppressed DBok-induced apoptosis but did not prevent DBok-induced cell death. Moreover, DBok targets mitochondria and triggers cytochrome c release through a caspase-independent mechanism. These characteristics of DBok reveal evolutionary conservation of cell death mechanisms in flies and humans.
authors.affiliation: Program on Apoptosis & Cell Death Regulation, Burnham Institute, La Jolla, California 92037, USA.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Huang
authors.forename: N
authors.initials: N
authors.lastname: Ke
authors.forename: S
authors.initials: S
authors.lastname: Matsuyama
authors.forename: B
authors.initials: B
authors.lastname: Hammock
authors.forename: A
authors.initials: A
authors.lastname: Godzik
authors.forename: J C
authors.initials: JC
authors.lastname: Reed
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers; D004330:Drosophila / Q000235:genetics*; D019143:Evolution, Molecular; D019254:Genes, bcl-2; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D017386:Sequence Homology, Amino Acid; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; D002352:Carrier Proteins; D017931:DNA Primers; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein