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

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)662-667
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number2
DOIs
Publication statusPublished - 2000 Jan 18
Externally publishedYes

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Drosophila
Cell Death
Caspases
Apoptosis
Caspase Inhibitors
Baculoviridae
Mitochondrial Membranes
Mitochondria
Proteins
Phenotype
Membranes
Ectopic Gene Expression

ASJC Scopus subject areas

  • Genetics
  • General

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Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death. / Igaki, Tatsushi; Kanuka, Hirotaka; Inohara, Naohiro; Sawamoto, Kazunobu; Núñez, Gabriel; Okano, Hideyuki; Miura, Masayuki.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 2, 18.01.2000, p. 662-667.

Research output: Contribution to journalArticle

Igaki, Tatsushi ; Kanuka, Hirotaka ; Inohara, Naohiro ; Sawamoto, Kazunobu ; Núñez, Gabriel ; Okano, Hideyuki ; Miura, Masayuki. / Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 2. pp. 662-667.
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