Abstract
Caspases, a group of cysteine proteases, constitute the effector arm of the cell death machinery. There are seven caspases known in Drosophila, three of which contain long amino-terminal prodomains. Although, compared to mammalian caspases, much less is known about the biology of Drosophila caspases, many studies have shown that caspases are essential for programmed cell death in the fly and are likely to be regulated in ways similar to their mammalian counterparts. Studies on fly caspases have revealed some new insights on cell death regulation. For example, the transcript for the fly caspase DRONC is regulated by the hormone ecdysone during programmed cell death in specific tissues. Recent data on DRONC also suggest that some fly caspases may have unique substrate specificities not ascribed to mammalian caspases. The presence of multiple caspases in Drosophila indicates that apoptotic pathways in insects are likely to be as complex as in vertebrates. Cell Death and Differentiation (2000) 7, 1039–1044.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Kumar S and Lavin MF . 1996 The ICE family of cysteine proteases as effectors of cell death. Cell Death Differ. 3: 255–267
Thornberry NA and Lazebnik Y . 1998 Caspases: enemies within. Science 281: 1312–1316
Cryns V and Yuan J . 1999 Proteases to die for. Genes Dev. 12: 1551–1570
Nicholson DW . 1999 Caspase structure, proteolytic substrates, and function during apoptotic cell death. Cell Death Differ. 6: 1028–1042
Ahmad M, Srinivasula SM, Wang L, Litwack G, Fernandes-Alnemri T and Alnemri ES . 1997 Spodoptera frugiperda caspase-1, a novel insect death protease that cleaves the nuclear immunophilin FKBP46, is the target of the baculovirus antiapoptotic protein p35. J. Biol. Chem. 272: 1421–1424
Song Z, McCall K and Steller H . 1997 DCP-1, a Drosophila cell death protease essential for development. Science 275: 536–540
Fraser AG and Evan GI . 1997 Identification of a Drosophila melanogaster ICE/CED-3-related protease, drICE. EMBO J. 16: 2805–2813
Chen P, Rodriguez A, Erskine R, Thach T and Abrams JM . 1998 Dredd, a novel effector of the apoptosis activators reaper, grim, and hid in Drosophila. Dev. Biol. 201: 202–216
Inohara N, Koseki T, Hu Y, Chen S and Núñez G . 1997 CLARP, a death effector domain containing protein interacts with caspase-8 and regulates apoptosis. Proc. Natl. Acad. Sci. USA 94: 10717–10722
Dorstyn L, Colussi PA, Quinn LM, Richardson H and Kumar S . 1999 DRONC, an ecdysone inducible Drosophila caspase. Proc. Natl. Acad. Sci. USA 96: 4307–4312
Dorstyn L, Read SH, Quinn LM, Richardson H and Kumar S . 1999 DECAY, a novel Drosophila caspase related to mammalian caspase-3 and caspase-7. J. Biol. Chem. 274: 30778–30783
Rubin GM, Yandell MD, Wortman JR, Miklos GLG, Nelson CR, Hariharan IK, Fortini ME, Li PW, Apweiler R, Fleischmann W, Cherry JM, Henikoff S, Skupski MP, Misra S, Ashburner M, Birney E, Boguski MS, Brody T, Brokstein P, Celniker SE, Chervitz SA, Coates D, Cravchik A, Gabrielian A, Galle RF, Gelbart WM, George RA, Goldstein LSB, Gong F, Guan P, Harris NL, Hay BA, Hoskins RA, Li J, Li Z, Hynes RO, Jones SJM, Kuehl PM, Lemaitre B, Littleton JT, Morrison DK, Mungall C, O'Farrell PH, Pickeral OK, Shue C, Vosshall LB, Zhang J, Zhao Q, Zheng XH, Zhong F, Zhong W, Gibbs R, Venter JC, Adams MC and Lewis S . 2000 Comparative genomics of the eukaryotes. Science 287: 2204–2215
Kumar S . 1999 Mechanisms mediating caspase activation in apoptosis. Cell Death Differ. 6: 1060–1066
Kumar S and Colussi PA . 1999 Prodomains-adaptors-oligomerization: the pursuit of caspase activation in apoptosis. Trends Biochem. Sci. 24: 1–4
Aravind L, Dixit VM and Koonin EV . 1999 The domains of death: evolution of apoptosis machinery. Trends Biochem. Sci. 24: 47–53
Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES and Wang X . 1997 Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91: 479–489
Zou H, Li Y, Liu X and Wang X . 1999 An APAF-1-cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J. Biol. Chem. 274: 11549–11556
Abrams JM, White K, Fessler LI and Steller H . 1993 Programmed cell death during Drosophila embryogenesis. Development 117: 29–43
McCall K and Steller H . 1998 Requirement for DCP-1 caspase during Drosophila oogenesis. Science 279: 230–234
Song Z, Guan B, Bergman A, Nicholson DW, Thornberry NA, Peterson EP and Steller H . 2000 Biochemical and genetic interactions between Drosophila caspases and the proapoptotic genes rpr, hid, and grim. Mol. Cell. Biol. 20: 2907–2914
Elrod-Erickson M, Misra S and Schneider D . 2000 Interaction between the cellular and humoral immune response in Drosophila. Curr. Biol. 10: 781–784
Fraser AG, McCarthy NJ and Evan GI . 1997 drICE is an essential caspase required for apoptotic activity in Drosophila cells. EMBO J. 16: 6192–6199
Meier P, Silke J, Leevers SJ and Evan GI . 2000 The Drosophila caspase DRONC is regulated by DIAPI. EMBO J. 19: 598–611
Hawkins CJ, Yoo SJ, Peterson EP, Wang SL, Vernooy SY and Hay BA . 2000 The Drosophila caspase DRONC is a glutamate/aspartate protease whose activity is regulated by DIAP1, HID and GRIM. J. Biol. Chem. 275: 27084–27093
Kanuka H, Sawamoto K, Inohara N, Matsuno K, Okano H and Miura M . 1999 Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator. Mol. Cell 4: 757–769
Yang X, Chang HY and Baltimore D . 1998 Essential role of CED-4 oligomerisation in CED-3 activation and apoptosis. Science. 281: 1355–1357
Rodriguez A, Oliver H, Zou H, Chen P, Wang X and Abrams JM . 1999 Dark is a Drosophila homologue of Apaf-1/CED-4 and functions in an evolutionarily conserved death pathway. Nat. Cell Biol. 1: 272–279
Zhou L, Song Z, Tittel J and Steller H . 1999 HAC-1, a Drosophila homolog of APAF-1 CED-4 functions in developmental and radiation-induced apoptosis. Mol. Cell 4: 745–755
Hawkins CJ, Wang SL and Hay BA . 1999 A cloning method to identify caspases and their regulators in yeast: Identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1. Proc. Natl. Acad. Sci. USA 96: 2885–2890
Kaiser WJ, Vucic D and Miller LK . 1998 The Drosophila inhibitor of apoptosis D-IAP1 suppresses cell death induced by the caspase drICE. FEBS Lett. 440: 243–248
Wang SL, Hawkins CJ, Yoo SJ, Muller HA and Hay BA . 1999 The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell 98: 453–463
Goyal L, MacCall K, Agapite J, Hartwieg E and Steller H . 2000 Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function. EMBO J. 19: 589–597
Green DR and Reed JC . 1998 Mitochondria and apoptosis. Science 281: 1309–1312
Li K, Li Y, Shelton JM, Richardson JA, Spencer E, Chen ZJ, Wang X and Williams RS . 2000 Cytochrome c deficiency causes embryonic lethality and attenuates stress-induced apoptosis. Cell 101: 389–399
Varkey J, Chen P, Jemmerson R and Abrams JM . 1999 Altered cytochrome c display precedes apoptotic cell death in Drosophila. J. Cell. Biol. 144: 701–710
Liu X, Zou H, Slaughter C and Wang X . 1997 DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89: 175–184
Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A and Nagata S . 1998 A caspase activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 391: 43–50
Yokoyama H, Mukae N, Sakahira H, Okawa K, Iwamatsu A and Nagata S . 2000 A novel activation mechanism of caspase-activated DNase from Drosophila melanogaster. J. Biol. Chem. 275: 12978–12986
LaCount DJ, Hanson SF, Schneider CL and Friesen PD . 2000 Caspase inhibitor P35 and inhibitor of apoptosis Op-IAP block in vivo proteolytic activation of an effector caspase at different steps. J. Biol. Chem. 275: 15657–15664
Acknowledgements
We thank John Abrams and Natasha Harvey for helpful comments and discussions. The work in our laboratory is supported by the Wellcome Trust and the National Health and Medical Council of Australia. S Kumar is a Wellcome Senior Fellow in Medical Science. J Doumanis is a Dawes Postgraduate Scholar.
Author information
Authors and Affiliations
Corresponding author
Additional information
Edited by G Melino
Rights and permissions
This article is cited by
-
Mutation and apoptosis are well-coordinated for protecting against DNA damage-inducing toxicity in Drosophila
Genes and Environment (2023)
-
An increase in mitochondrial TOM activates apoptosis to drive retinal neurodegeneration
Scientific Reports (2022)
-
Up-regulation of apoptotic- and cell survival-related gene pathways following exposures of western corn rootworm to B. thuringiensis crystalline pesticidal proteins in transgenic maize roots
BMC Genomics (2021)
-
Initiator and executioner caspases in salivary gland apoptosis of Rhipicephalus haemaphysaloides
Parasites & Vectors (2020)
-
Accurate elimination of superfluous attachment cells is critical for the construction of functional multicellular proprioceptors in Drosophila
Cell Death & Differentiation (2019)


