Role of Bcl-2 family members in invertebrates.
Proteins belonging to the Bcl-2 family function as regulators of 'life-or-death' decisions in response to various intrinsic and extrinsic stimuli. In mammals, cell death is controlled by pro- and anti-apoptotic members of the Bcl-2 family, which function upstream of the caspase cascade. Structural and functional homologues of the Bcl-2 family proteins also exist in lower eukaryotes, such as nematodes and flies. In nematodes, an anti-apoptotic Bcl-2 family protein, CED-9, functions as a potent cell death inhibitor, and a BH3-only protein, EGL-1, acts as an inhibitor of CED-9 to facilitate the spatio-temporal regulation of programmed cell death. On the other hand, the Drosophila genome encodes two Bcl-2 family proteins, Drob-1/Debcl/dBorg-1/dBok and Buffy/dBorg-2, both of which structurally belong to the pro-apoptotic group, despite abundant similarities in the cell death mechanisms between flies and vertebrates. Drob-1 acts as a pro-apoptotic factor in vitro and in vivo, and Buffy/dBorg-2 exhibits a weak anti-apoptotic function. The ancestral role of the Bcl-2 family protein may be pro-apoptotic, and the evolution of the functions of this family of proteins may be closely linked with the contribution of mitochondria to the cell death pathway.
Igaki
Tatsushi
T
Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan.
Miura
Masayuki
M
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D005075:Biological Evolution; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D029721:Drosophila Proteins / Q000502:physiology; D007448:Invertebrates / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D019253:Proto-Oncogene Proteins c-bcl-2