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 Núñez, Hideyuki Okano, Masayuki Miura

研究成果: Article査読

128 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)662-667
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
97
2
DOI
出版ステータスPublished - 2000 1 18
外部発表はい

ASJC Scopus subject areas

  • General

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