Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim

In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previous...

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Main Authors: Song, Zhiwei, Guan, Bo, Bergman, Andreas, Nicholson, Donald W., Thornberry, Nancy A., Peterson, Erin P., Steller, Hermann
Formato: Artigo
Idioma:en
Publicado em: American Society for Microbiology 2000
Assuntos:
Cell Growth and Development
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC85526/
https://ncbi.nlm.nih.gov/pubmed/10733594
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spelling pubmed-855262002-09-13 Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim Song, Zhiwei Guan, Bo Bergman, Andreas Nicholson, Donald W. Thornberry, Nancy A. Peterson, Erin P. Steller, Hermann Mol Cell Biol Cell Growth and Development In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified. We now show that DCP-1 has a substrate specificity that is remarkably similar to those of human caspase 3 and Caenorhabditis elegans CED-3, suggesting that DCP-1 is a death effector caspase. drICE and DCP-1 have similar yet different enzymatic specificities. Although expression of either in cultured cells induces apoptosis, neither protein was able to induce DNA fragmentation in Drosophila SL2 cells. Ectopic expression of a truncated form of dcp-1 (ΔN-dcp-1) in the developing Drosophila retina under an eye-specific promoter resulted in a small and rough eye phenotype, whereas expression of the full-length dcp-1 (fl-dcp-1) had little effect. On the other hand, expression of either full-length drICE (fl-drICE) or truncated drICE (ΔN-drICE) in the retina showed no obvious eye phenotype. Although active DCP-1 protein cleaves full-length DCP-1 and full-length drICE in vitro, GMR-ΔN-dcp-1 did not enhance the eye phenotype of GMR-fl-dcp-1 or GMR-fl-drICE flies. Significantly, GMR-rpr and GMR-grim, but not GMR-hid, dramatically enhanced the eye phenotype of GMR-fl-dcp-1 flies. These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo. American Society for Microbiology 2000-04 /pmc/articles/PMC85526/ /pubmed/10733594 Text en Copyright © 2000, American Society for Microbiology
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Cell Growth and Development
spellingShingle Cell Growth and Development
Song, Zhiwei
Guan, Bo
Bergman, Andreas
Nicholson, Donald W.
Thornberry, Nancy A.
Peterson, Erin P.
Steller, Hermann
Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim
description In Drosophila melanogaster, the induction of apoptosis requires three closely linked genes, reaper (rpr), head involution defective (hid), and grim. The products of these genes induce apoptosis by activating a caspase pathway. Two very similar Drosophila caspases, DCP-1 and drICE, have been previously identified. We now show that DCP-1 has a substrate specificity that is remarkably similar to those of human caspase 3 and Caenorhabditis elegans CED-3, suggesting that DCP-1 is a death effector caspase. drICE and DCP-1 have similar yet different enzymatic specificities. Although expression of either in cultured cells induces apoptosis, neither protein was able to induce DNA fragmentation in Drosophila SL2 cells. Ectopic expression of a truncated form of dcp-1 (ΔN-dcp-1) in the developing Drosophila retina under an eye-specific promoter resulted in a small and rough eye phenotype, whereas expression of the full-length dcp-1 (fl-dcp-1) had little effect. On the other hand, expression of either full-length drICE (fl-drICE) or truncated drICE (ΔN-drICE) in the retina showed no obvious eye phenotype. Although active DCP-1 protein cleaves full-length DCP-1 and full-length drICE in vitro, GMR-ΔN-dcp-1 did not enhance the eye phenotype of GMR-fl-dcp-1 or GMR-fl-drICE flies. Significantly, GMR-rpr and GMR-grim, but not GMR-hid, dramatically enhanced the eye phenotype of GMR-fl-dcp-1 flies. These results indicate that Reaper and Grim, but not HID, can activate DCP-1 in vivo.
author Song, Zhiwei
Guan, Bo
Bergman, Andreas
Nicholson, Donald W.
Thornberry, Nancy A.
Peterson, Erin P.
Steller, Hermann
author_facet Song, Zhiwei
Guan, Bo
Bergman, Andreas
Nicholson, Donald W.
Thornberry, Nancy A.
Peterson, Erin P.
Steller, Hermann
author_sort Song, Zhiwei
title Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim
title_short Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim
title_full Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim
title_fullStr Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim
title_full_unstemmed Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim
title_sort biochemical and genetic interactions between drosophila caspases and the proapoptotic genes rpr, hid, and grim
publisher American Society for Microbiology
publisher_facet American Society for Microbiology
publishDate 2000
url https://ncbi.nlm.nih.gov/pmc/articles/PMC85526/
https://ncbi.nlm.nih.gov/pubmed/10733594
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