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Gene Review

Nc  -  Nedd2-like caspase

Drosophila melanogaster

Synonyms: CG8090, CG8091, Caspase Nc, DRONC, Dmel\CG8091, ...
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Disease relevance of Nc

  • In Drosophila, the caspase-9 counterpart Dronc is essential for most apoptotic death, whereas the caspase-8 homolog Dredd activates NF-kappaB signaling in response to gram-negative bacterial infection [1].
  • These mutants present a range of defects, including extensive hyperplasia of hematopoietic tissues, supernumerary neuronal cells, and head involution failure. dronc genetically interacts with the Ced4/Apaf1 counterpart, Dark, and adult structures lacking dronc are disrupted for fine patterning [2].

High impact information on Nc

  • These results indicate an apoptosis-independent role for DIAP1-mediated Dronc inhibition in Rac-mediated cell motility [3].
  • This allows for local activation of the Dronc caspase, thereby preserving C4da neurons while severing their dendrites [4].
  • Furthermore, orthologues of the apoptosome components, Ark (Apaf-1) and Dronc (caspase-9), are also required for the proper removal of bulk cytoplasm during spermatogenesis [5].
  • However, unlike caspase activation in mammals, DRONC activation is not accompanied by the release of cytochrome c from mitochondria [6].
  • Finally, we show that the dronc promoter has BR-C interaction sites, and that it can be transactivated by a specific isoform of BR-C [7].

Biological context of Nc


Anatomical context of Nc

  • In late third instar larvae, dronc mRNA is dramatically up-regulated in salivary glands and midgut before histolysis of these tissues [11].

Associations of Nc with chemical compounds

  • These results suggest that DRONC is an effector of steroid-mediated apoptosis during insect metamorphosis [11].
  • In both living and dying S2 cells, DIAP1 is cleaved by DRONC after glutamate residue Glu-205, located between the first and second BIR domains [12].
  • DRONC prefers tetrapeptide substrates in which aliphatic amino acids are present at the P2 position, and the P1 residue can be either aspartate or glutamate [13].

Physical interactions of Nc

  • This recognition is essential for DIAP1 binding to Dronc, and for targeting Dronc for ubiquitination [14].

Regulatory relationships of Nc


Other interactions of Nc

  • DRONC, a key apical caspase in Drosophila, is the only known caspase that is transcriptionally regulated by ecdysone during development [7].
  • Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity [17].
  • Dying midguts express the rpr, hid, ark, dronc, and crq cell death genes, suggesting that the core cell death machinery is involved in larval midgut cell death [18].
  • A significant proportion of cellular DRONC and DRICE appears to localize near mitochondria, suggesting that an apoptosome may form in the vicinity of mitochondria in the absence of cytochrome c release [19].
  • Dronc also interacts, both genetically and biochemically, with the CED-4/Apaf-1 fly homolog, Dark [15].


  1. Interactions of DNR1 with the apoptotic machinery of Drosophila melanogaster. Primrose, D.A., Chaudhry, S., Johnson, A.G., Hrdlicka, A., Schindler, A., Tran, D., Foley, E. J. Cell. Sci. (2007) [Pubmed]
  2. The apical caspase dronc governs programmed and unprogrammed cell death in Drosophila. Chew, S.K., Akdemir, F., Chen, P., Lu, W.J., Mills, K., Daish, T., Kumar, S., Rodriguez, A., Abrams, J.M. Dev. Cell (2004) [Pubmed]
  3. A role for Drosophila IAP1-mediated caspase inhibition in Rac-dependent cell migration. Geisbrecht, E.R., Montell, D.J. Cell (2004) [Pubmed]
  4. Identification of E2/E3 ubiquitinating enzymes and caspase activity regulating Drosophila sensory neuron dendrite pruning. Kuo, C.T., Zhu, S., Younger, S., Jan, L.Y., Jan, Y.N. Neuron (2006) [Pubmed]
  5. The two Drosophila cytochrome C proteins can function in both respiration and caspase activation. Arama, E., Bader, M., Srivastava, M., Bergmann, A., Steller, H. EMBO J. (2006) [Pubmed]
  6. The two cytochrome c species, DC3 and DC4, are not required for caspase activation and apoptosis in Drosophila cells. Dorstyn, L., Mills, K., Lazebnik, Y., Kumar, S. J. Cell Biol. (2004) [Pubmed]
  7. Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex. Cakouros, D., Daish, T., Martin, D., Baehrecke, E.H., Kumar, S. J. Cell Biol. (2002) [Pubmed]
  8. The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. Wilson, R., Goyal, L., Ditzel, M., Zachariou, A., Baker, D.A., Agapite, J., Steller, H., Meier, P. Nat. Cell Biol. (2002) [Pubmed]
  9. The Drosophila caspase DRONC is regulated by DIAP1. Meier, P., Silke, J., Leevers, S.J., Evan, G.I. EMBO J. (2000) [Pubmed]
  10. The fly caspases. Kumar, S., Doumanis, J. Cell Death Differ. (2000) [Pubmed]
  11. DRONC, an ecdysone-inducible Drosophila caspase. Dorstyn, L., Colussi, P.A., Quinn, L.M., Richardson, H., Kumar, S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  12. Cleavage of the apoptosis inhibitor DIAP1 by the apical caspase DRONC in both normal and apoptotic Drosophila cells. Muro, I., Means, J.C., Clem, R.J. J. Biol. Chem. (2005) [Pubmed]
  13. The Drosophila caspase DRONC cleaves following glutamate or aspartate and is regulated by DIAP1, HID, and GRIM. Hawkins, C.J., Yoo, S.J., Peterson, E.P., Wang, S.L., Vernooy, S.Y., Hay, B.A. J. Biol. Chem. (2000) [Pubmed]
  14. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Chai, J., Yan, N., Huh, J.R., Wu, J.W., Li, W., Hay, B.A., Shi, Y. Nat. Struct. Biol. (2003) [Pubmed]
  15. An essential role for the caspase dronc in developmentally programmed cell death in Drosophila. Quinn, L.M., Dorstyn, L., Mills, K., Colussi, P.A., Chen, P., Coombe, M., Abrams, J., Kumar, S., Richardson, H. J. Biol. Chem. (2000) [Pubmed]
  16. Three-dimensional structure of a double apoptosome formed by the Drosophila Apaf-1 related killer. Yu, X., Wang, L., Acehan, D., Wang, X., Akey, C.W. J. Mol. Biol. (2006) [Pubmed]
  17. Compensatory proliferation in Drosophila imaginal discs requires Dronc-dependent p53 activity. Wells, B.S., Yoshida, E., Johnston, L.A. Curr. Biol. (2006) [Pubmed]
  18. Steroid regulation of midgut cell death during Drosophila development. Lee, C.Y., Cooksey, B.A., Baehrecke, E.H. Dev. Biol. (2002) [Pubmed]
  19. The role of cytochrome c in caspase activation in Drosophila melanogaster cells. Dorstyn, L., Read, S., Cakouros, D., Huh, J.R., Hay, B.A., Kumar, S. J. Cell Biol. (2002) [Pubmed]
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