This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Song, Z.
Right arrow Articles by Steller, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Song, Z.
Right arrow Articles by Steller, H.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2000, p. 2907-2914, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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

Zhiwei Song,1 Bo Guan,1 Andreas Bergman,1 Donald W. Nicholson,2 Nancy A. Thornberry,2 Erin P. Peterson,2 and Hermann Steller1,*

Departments of Biology and Brain and Cognitive Sciences, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139,1 and Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research, Pointe Claire, Dorval, Quebec H9R 4P8, Canada2

Received 8 October 1999/Returned for modification 10 November 1999/Accepted 11 January 2000

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 (Delta N-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 (Delta N-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-Delta N-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.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, Massachusetts Institute of Technology, Departments of Biology and Brain and Cognitive Sciences, 77 Massachusetts Ave., 68-430, Cambridge, MA 02139. Phone: (617) 253-6359. Fax: (617) 258-9430. E-mail: hsteller{at}mit.edu.

Molecular and Cellular Biology, April 2000, p. 2907-2914, Vol. 20, No. 8
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ribeiro, P. S., Kuranaga, E., Tenev, T., Leulier, F., Miura, M., Meier, P. (2007). DIAP2 functions as a mechanism-based regulator of drICE that contributes to the caspase activity threshold in living cells. JCB 179: 1467-1480 [Abstract] [Full Text]  
  • Yi, C. H., Sogah, D. K., Boyce, M., Degterev, A., Christofferson, D. E., Yuan, J. (2007). A genome-wide RNAi screen reveals multiple regulators of caspase activation. JCB 179: 619-626 [Abstract] [Full Text]  
  • Chandraratna, D., Lawrence, N., Welchman, D. P., Sanson, B. (2007). An in vivo model of apoptosis: linking cell behaviours and caspase substrates in embryos lacking DIAP1. J. Cell Sci. 120: 2594-2608 [Abstract] [Full Text]  
  • Anderson, J., Bhandari, R., Kumar, J. P. (2005). A Genetic Screen Identifies Putative Targets and Binding Partners of CREB-Binding Protein in the Developing Drosophila Eye. Genetics 171: 1655-1672 [Abstract] [Full Text]  
  • Yokokura, T., Dresnek, D., Huseinovic, N., Lisi, S., Abdelwahid, E., Bangs, P., White, K. (2004). Dissection of DIAP1 Functional Domains via a Mutant Replacement Strategy. J. Biol. Chem. 279: 52603-52612 [Abstract] [Full Text]  
  • Kohyama-Koganeya, A., Sasamura, T., Oshima, E., Suzuki, E., Nishihara, S., Ueda, R., Hirabayashi, Y. (2004). Drosophila Glucosylceramide Synthase: A NEGATIVE REGULATOR OF CELL DEATH MEDIATED BY PROAPOPTOTIC FACTORS. J. Biol. Chem. 279: 35995-36002 [Abstract] [Full Text]  
  • Laundrie, B., Peterson, J. S., Baum, J. S., Chang, J. C., Fileppo, D., Thompson, S. R., McCall, K. (2003). Germline Cell Death Is Inhibited by P-Element Insertions Disrupting the dcp-1/pita Nested Gene Pair in Drosophila. Genetics 165: 1881-1888 [Abstract] [Full Text]  
  • Peterson, C., Carney, G. E., Taylor, B. J., White, K. (2003). reaper is required for neuroblast apoptosis during Drosophila development. Development 129: 1467-1476 [Abstract] [Full Text]  
  • Hunter, A. M., Kottachchi, D., Lewis, J., Duckett, C. S., Korneluk, R. G., Liston, P. (2003). A Novel Ubiquitin Fusion System Bypasses the Mitochondria and Generates Biologically Active Smac/DIABLO. J. Biol. Chem. 278: 7494-7499 [Abstract] [Full Text]  
  • Arnt, C. R., Chiorean, M. V., Heldebrant, M. P., Gores, G. J., Kaufmann, S. H. (2002). Synthetic Smac/DIABLO Peptides Enhance the Effects of Chemotherapeutic Agents by Binding XIAP and cIAP1 in Situ. J. Biol. Chem. 277: 44236-44243 [Abstract] [Full Text]  
  • Ekert, P. G., Silke, J., Hawkins, C. J., Verhagen, A. M., Vaux, D. L. (2001). Diablo Promotes Apoptosis by Removing Miha/Xiap from Processed Caspase 9. JCB 152: 483-490 [Abstract] [Full Text]  
  • Heinrich, J. C., Scott, M. J. (2000). A repressible female-specific lethal genetic system for making transgenic insect strains suitable for a sterile-release program. Proc. Natl. Acad. Sci. USA 10.1073/pnas.140142697v1 [Abstract] [Full Text]  
  • Hawkins, C. J., Yoo, S. J., Peterson, E. P., Wang, S. L., Vernooy, S. Y., Hay, B. A. (2000). The Drosophila Caspase DRONC Cleaves following Glutamate or Aspartate and Is Regulated by DIAP1, HID, and GRIM. J. Biol. Chem. 275: 27084-27093 [Abstract] [Full Text]  
  • Heinrich, J. C., Scott, M. J. (2000). A repressible female-specific lethal genetic system for making transgenic insect strains suitable for a sterile-release program. Proc. Natl. Acad. Sci. USA 97: 8229-8232 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»