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Drob-1, a Drosophila Member of the Bcl-2/CED-9 Family That Promotes Cell Death
Tatsushi Igaki, Hirotaka Kanuka, Naohiro Inohara, Kazunobu Sawamoto, Gabriel Nunez, Hideyuki Okano and Masayuki Miura
Proceedings of the National Academy of Sciences of the United States of America
Vol. 97, No. 2 (Jan. 18, 2000), pp. 662-667
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/121679
Page Count: 6
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The Bcl-2/CED-9 family of proteins, which includes both antiapoptotic and proapoptotic members, plays key regulating roles in programmed cell death. We report here the identification and characterization of Drob-1, the first Drosophila member of the Bcl-2/CED-9 family to be isolated. Drob-1 contains four conserved Bcl-2 homology domains (BH1, BH2, BH3, and BH4) and a C-terminal hydrophobic domain. Ectopic expression of Drob-1 in the developing Drosophila eye resulted in a rough-eye phenotype. Furthermore, when overexpressed in Drosophila S2 cells, Drob-1 induced apoptosis accompanied by elevated caspase activity. This Drob-1-induced cell death, however, could not be antagonized by baculovirus p35, a broad-spectrum caspase inhibitor. Drob-1 was localized to the intracytoplasmic membranes, predominantly to the mitochondrial membranes, and a mutant Drob-1 lacking the hydrophobic C terminus lost both its mitochondrial localization and its proapoptotic activity. These results suggest that Drob-1 promotes cell death by inducing both caspase-dependent and -independent pathways at the mitochondria. Our identification of Drob-1 and further genetic analysis should provide increased understanding of the universal mechanisms by which the Bcl-2/CED-9 family members and other related proteins regulate apoptosis.
Proceedings of the National Academy of Sciences of the United States of America © 2000 National Academy of Sciences