Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 9 February 1996:
Vol. 271. no. 5250, pp. 805 - 807
DOI: 10.1126/science.271.5250.805

Reports

Cell Killing by the Drosophila Gene reaper

Kristin White,  Elvan Tahaoglu,  Hermann Steller

The reaper gene (rpr) is important for the activation of apoptosis in Drosophila. To investigate whether rpr expression is sufficient to induce apoptosis, transgenic flies were generated that express rpr complementary DNA or the rpr open reading frame in cells that normally live. Transcription of rpr from a heat-inducible promoter rapidly caused widespread ectopic apoptosis and organismal death. Ectopic overexpression of rpr in the developing retina resulted in eye ablation. The occurrence of cell death was highly sensitive to the dosage of the transgene. Because cell death induced by the protein encoded by rpr (RPR) could be blocked by the baculovirus p35 protein, RPR appears to activate a death program mediated by a ced-3/ICE (interleukin-1 converting enzyme)-like protease.


K. White and E. Tahaoglu, Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
H. Steller, Howard Hughes Medical Institute and the Departments of Brain and Cognitive Sciences and Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Developmentally Active and Stress-Inducible Noncoding hsr{omega} Gene Is a Novel Regulator of Apoptosis in Drosophila.
M. Mallik and S. C. Lakhotia (2009)
Genetics 183, 831-852
   Abstract »    Full Text »    PDF »
Antagonistic roles for Ultrabithorax and Antennapedia in regulating segment-specific apoptosis of differentiated motoneurons in the Drosophila embryonic central nervous system.
A. Rogulja-Ortmann, S. Renner, and G. M. Technau (2008)
Development 135, 3435-3445
   Abstract »    Full Text »    PDF »
Efficient Ends-Out Gene Targeting In Drosophila.
J. Huang, W. Zhou, A. M. Watson, Y.-N. Jan, and Y. Hong (2008)
Genetics 180, 703-707
   Abstract »    Full Text »    PDF »
Mutations in String/CDC25 inhibit cell cycle re-entry and neurodegeneration in a Drosophila model of Ataxia telangiectasia.
S. A. Rimkus, R. J. Katzenberger, A. T. Trinh, G. E. Dodson, R. S. Tibbetts, and D. A. Wassarman (2008)
Genes & Dev. 22, 1205-1220
   Abstract »    Full Text »    PDF »
Microarray Analysis of Replicate Populations Selected Against a Wing-Shape Correlation in Drosophila melanogaster.
K. E. Weber, R. J. Greenspan, D. R. Chicoine, K. Fiorentino, M. H. Thomas, and T. L. Knight (2008)
Genetics 178, 1093-1108
   Abstract »    Full Text »    PDF »
Mitochondrial Localization of Reaper to Promote Inhibitors of Apoptosis Protein Degradation Conferred by GH3 Domain-Lipid Interactions.
C. D. Freel, D. A. Richardson, M. J. Thomenius, E. C. Gan, S. R. Horn, M. R. Olson, and S. Kornbluth (2008)
J. Biol. Chem. 283, 367-379
   Abstract »    Full Text »    PDF »
Down-regulation of inhibitor of apoptosis levels provides competence for steroid-triggered cell death.
V. P. Yin, C. S. Thummel, and A. Bashirullah (2007)
J. Cell Biol. 178, 85-92
   Abstract »    Full Text »    PDF »
Interactions of DNR1 with the apoptotic machinery of Drosophila melanogaster.
D. A. Primrose, S. Chaudhry, A. G. D. Johnson, A. Hrdlicka, A. Schindler, D. Tran, and E. Foley (2007)
J. Cell Sci. 120, 1189-1199
   Abstract »    Full Text »    PDF »
The Trithorax group protein Lid is a trimethyl histone H3K4 demethylase required for dMyc-induced cell growth.
J. Secombe, L. Li, L. Carlos, and R. N. Eisenman (2007)
Genes & Dev. 21, 537-551
   Abstract »    Full Text »    PDF »
Eukaryotic operon-like transcription of functionally related genes in Drosophila.
Y. Ben-Shahar, K. Nannapaneni, T. L. Casavant, T. E. Scheetz, and M. J. Welsh (2007)
PNAS 104, 222-227
   Abstract »    Full Text »    PDF »
The Ral/Exocyst Effector Complex Counters c-Jun N-Terminal Kinase-Dependent Apoptosis in Drosophila melanogaster.
M. Balakireva, C. Rosse, J. Langevin, Y.-c. Chien, M. Gho, G. Gonzy-Treboul, S. Voegeling-Lemaire, S. Aresta, J.-A. Lepesant, Y. Bellaiche, et al. (2006)
Mol. Cell. Biol. 26, 8953-8963
   Abstract »    Full Text »    PDF »
A Gradient of Epidermal Growth Factor Receptor Signaling Determines the Sensitivity of rbf1 Mutant Cells to E2F-Dependent Apoptosis.
N.-S. Moon, L. Di Stefano, and N. Dyson (2006)
Mol. Cell. Biol. 26, 7601-7615
   Abstract »    Full Text »    PDF »
DRONC Coordinates Cell Death and Compensatory Proliferation..
S. Kondo, N. Senoo-Matsuda, Y. Hiromi, and M. Miura (2006)
Mol. Cell. Biol. 26, 7258-7268
   Abstract »    Full Text »    PDF »
Organization of the peripheral fly eye: the roles of Snail family transcription factors in peripheral retinal apoptosis.
H.-Y. Lim and A. Tomlinson (2006)
Development 133, 3529-3537
   Abstract »    Full Text »    PDF »
The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process.
I. Muro, D. L. Berry, J. R. Huh, C. H. Chen, H. Huang, S. J. Yoo, M. Guo, E. H. Baehrecke, and B. A. Hay (2006)
Development 133, 3305-3315
   Abstract »    Full Text »    PDF »
Mis-specified cells die by an active gene-directed process, and inhibition of this death results in cell fate transformation in Drosophila.
C. Werz, T. V. Lee, P. L. Lee, M. Lackey, C. Bolduc, D. S. Stein, and A. Bergmann (2005)
Development 132, 5343-5352
   Abstract »    Full Text »    PDF »
Genetic Modifier Screens on Hairless Gain-of-Function Phenotypes Reveal Genes Involved in Cell Differentiation, Cell Growth and Apoptosis in Drosophila melanogaster.
D. Muller, S. J. Kugler, A. Preiss, D. Maier, and A. C. Nagel (2005)
Genetics 171, 1137-1152
   Abstract »    Full Text »    PDF »
The CARD-carrying caspase Dronc is essential for most, but not all, developmental cell death in Drosophila.
D. Xu, Y. Li, M. Arcaro, M. Lackey, and A. Bergmann (2005)
Development 132, 2125-2134
   Abstract »    Full Text »    PDF »
Dissection of DIAP1 Functional Domains via a Mutant Replacement Strategy.
T. Yokokura, D. Dresnek, N. Huseinovic, S. Lisi, E. Abdelwahid, P. Bangs, and K. White (2004)
J. Biol. Chem. 279, 52603-52612
   Abstract »    Full Text »    PDF »
Translating Available Food Into the Number of Eggs Laid by Drosophila melanogaster.
J. Terashima and M. Bownes (2004)
Genetics 167, 1711-1719
   Abstract »    Full Text »    PDF »
A balance between the diap1 death inhibitor and reaper and hid death inducers controls steroid-triggered cell death in Drosophila.
V. P. Yin and C. S. Thummel (2004)
PNAS 101, 8022-8027
   Abstract »    Full Text »    PDF »
Hemolymph Sugar Homeostasis and Starvation-Induced Hyperactivity Affected by Genetic Manipulations of the Adipokinetic Hormone-Encoding Gene in Drosophila melanogaster.
G. Lee and J. H. Park (2004)
Genetics 167, 311-323
   Abstract »    Full Text »    PDF »
Genome-Wide RNAi Analysis of Growth and Viability in Drosophila Cells.
M. Boutros, A. A. Kiger, S. Armknecht, K. Kerr, M. Hild, B. Koch, S. A. Haas, H. F. A. Consortium, R. Paro, and N. Perrimon (2004)
Science 303, 832-835
   Abstract »    Full Text »    PDF »
Drosophila melanogaster MNK/Chk2 and p53 Regulate Multiple DNA Repair and Apoptotic Pathways following DNA Damage.
M. H. Brodsky, B. T. Weinert, G. Tsang, Y. S. Rong, N. M. McGinnis, K. G. Golic, D. C. Rio, and G. M. Rubin (2004)
Mol. Cell. Biol. 24, 1219-1231
   Abstract »    Full Text »    PDF »
Limited Role of Developmental Programmed Cell Death Pathways in Drosophila norpA Retinal Degeneration.
C.-D. Hsu, M. A. Whaley, K. Frazer, D. A. Miller, K. A. Mitchell, S. M. Adams, and J. E. O'Tousa (2004)
J. Neurosci. 24, 500-507
   Abstract »    Full Text »    PDF »
DIAP1 suppresses ROS-induced apoptosis caused by impairment of the selD/sps1 homolog in Drosophila.
M. Morey, M. Corominas, and F. Serras (2003)
J. Cell Sci. 116, 4597-4604
   Abstract »    Full Text »    PDF »
A GH3-like Domain in Reaper Is Required for Mitochondrial Localization and Induction of IAP Degradation.
M. R. Olson, C. L. Holley, E. C. Gan, D. A. Colon-Ramos, B. Kaplan, and S. Kornbluth (2003)
J. Biol. Chem. 278, 44758-44768
   Abstract »    Full Text »    PDF »
senseless is necessary for the survival of embryonic salivary glands in Drosophila.
V. Chandrasekaran and S. K. Beckendorf (2003)
Development 130, 4719-4728
   Abstract »    Full Text »    PDF »
Targeted ablation of CCAP neuropeptide-containing neurons of Drosophila causes specific defects in execution and circadian timing of ecdysis behavior.
J. H. Park, A. J. Schroeder, C. Helfrich-Forster, F. R. Jackson, and J. Ewer (2003)
Development 130, 2645-2656
   Abstract »    Full Text »    PDF »
A positive role for Patched-Smoothened signaling in promoting cell proliferation during normal head development in Drosophila.
B. V. Shyamala and K. M. Bhat (2003)
Development 129, 1839-1847
   Abstract »    Full Text »    PDF »
reaper is required for neuroblast apoptosis during Drosophila development.
C. Peterson, G. E. Carney, B. J. Taylor, and K. White (2003)
Development 129, 1467-1476
   Abstract »    Full Text »    PDF »
Apoptosis-mediated cell death within the ovarian polar cell lineage of Drosophila melanogaster.
F. Besse and A.-M. Pret (2003)
Development 130, 1017-1027
   Abstract »    Full Text »    PDF »
Reaper Is Regulated by IAP-mediated Ubiquitination.
M. R. Olson, C. L. Holley, S. J. Yoo, J. R. Huh, B. A. Hay, and S. Kornbluth (2003)
J. Biol. Chem. 278, 4028-4034
   Abstract »    Full Text »    PDF »
Drosophila myb exerts opposing effects on S phase, promoting proliferation and suppressing endoreduplication.
C. A. Fitzpatrick, N. V. Sharkov, G. Ramsay, and A. L. Katzen (2002)
Development 129, 4497-4507
   Abstract »    Full Text »    PDF »
Steroid regulation of autophagic programmed cell death during development.
C. Lee and E. Baehrecke (2001)
Development 128, 1443-1455
   Abstract »    PDF »
Hindgut visceral mesoderm requires an ectodermal template for normal development in Drosophila.
B San Martin and M Bate (2001)
Development 128, 233-242
   Abstract »    PDF »
Identification and characterization of a p53 homologue in Drosophila melanogaster.
S. Jin, S. Martinek, W. S. Joo, J. R. Wortman, N. Mirkovic, A. Sali, M. D. Yandell, N. P. Pavletich, M. W. Young, and A. J. Levine (2000)
PNAS 97, 7301-7306
   Abstract »    Full Text »    PDF »
Biochemical and Genetic Interactions between Drosophila Caspases and the Proapoptotic Genes rpr, hid, and grim.
Z. Song, B. Guan, A. Bergman, D. W. Nicholson, N. A. Thornberry, E. P. Peterson, and H. Steller (2000)
Mol. Cell. Biol. 20, 2907-2914
   Abstract »    Full Text »
Diverse Domains of THREAD/DIAP1 Are Required to Inhibit Apoptosis Induced by REAPER and HID in Drosophila.
S. Lisi, I. Mazzon, and K. White (2000)
Genetics 154, 669-678
   Abstract »    Full Text »
Drob-1, a Drosophila member of the Bcl-2/CED-9 family that promotes cell death.
T. Igaki, H. Kanuka, N. Inohara, K. Sawamoto, G. Nunez, H. Okano, and M. Miura (2000)
PNAS 97, 662-667
   Abstract »    Full Text »    PDF »
Glia maintain follower neuron survival during Drosophila CNS development.
G. Booth, E. Kinrade, and A Hidalgo (2000)
Development 127, 237-244
   Abstract »    PDF »
Genetic Dissection of Behavior: Modulation of Locomotion by Light in the Drosophila melanogaster Larva Requires Genetically Distinct Visual System Functions.
M. Busto, B. Iyengar, and A. R. Campos (1999)
J. Neurosci. 19, 3337-3344
   Abstract »    Full Text »    PDF »
The proapoptotic function of Drosophila Hid is conserved in mammalian cells.
W. N. Haining, C. Carboy-Newcomb, C. L. Wei, and H. Steller (1999)
PNAS 96, 4936-4941
   Abstract »    Full Text »    PDF »
Altered Cytochrome c Display Precedes Apoptotic Cell Death in Drosophila.
J. Varkey, P. Chen, R. Jemmerson, and J. M. Abrams (1999)
J. Cell Biol. 144, 701-710
   Abstract »    Full Text »    PDF »
PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development.
H Huang, C. Potter, W Tao, D. Li, W Brogiolo, E Hafen, H Sun, and T Xu (1999)
Development 126, 5365-5372
   Abstract »    PDF »
Proapoptotic activity of Caenorhabditis elegans CED-4 protein in Drosophila: Implicated mechanisms for caspase activation.
H. Kanuka, S. Hisahara, K. Sawamoto, S.-i. Shoji, H. Okano, and M. Miura (1999)
PNAS 96, 145-150
   Abstract »    Full Text »    PDF »
Ceramide Generation by the Reaper Protein Is Not Blocked by the Caspase Inhibitor, p35.
R. Bose, P. Chen, A. Loconti, C. Grullich, J. M. Abrams, and R. N. Kolesnick (1998)
J. Biol. Chem. 273, 28852-28859
   Abstract »    Full Text »    PDF »
Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels.
V. Avdonin, J. Kasuya, M. A. Ciorba, B. Kaplan, T. Hoshi, and L. Iverson (1998)
PNAS 95, 11703-11708
   Abstract »    Full Text »    PDF »
Apoptosis Induced by Drosophila Reaper and Grim in a Human System. ATTENUATION BY INHIBITOR OF APOPTOSIS PROTEINS (cIAPs).
J. V. McCarthy and V. M. Dixit (1998)
J. Biol. Chem. 273, 24009-24015
   Abstract »    Full Text »    PDF »
Inhibitor of Apoptosis Proteins Physically Interact with and Block Apoptosis Induced by Drosophila Proteins HID and GRIM.
D. Vucic, W. J. Kaiser, and L. K. Miller (1998)
Mol. Cell. Biol. 18, 3300-3309
   Abstract »    Full Text »
Galpha s-Induced Neurodegeneration in Caenorhabditis elegans.
A. J. Berger, A. C. Hart, and J. M. Kaplan (1998)
J. Neurosci. 18, 2871-2880
   Abstract »    Full Text »    PDF »
Toxoplasma gondii-Infected Cells Are Resistant to Multiple Inducers of Apoptosis.
P. B. Nash, M. B. Purner, R. P. Leon, P. Clarke, R. C. Duke, and T. J. Curiel (1998)
J. Immunol. 160, 1824-1830
   Abstract »    Full Text »    PDF »
Caenorhabditis elegans anti-apoptotic gene ced-9 prevents ced-3-induced cell death in Drosophila cells.
S Hisahara, H Kanuka, S Shoji, S Yoshikawa, H Okano, and M Miura (1998)
J. Cell Sci. 111, 667-673
   Abstract »    PDF »
Cell-specific Induction of Apoptosis by Microinjection of Cytochrome c. Bcl-xL HAS ACTIVITY INDEPENDENT OF CYTOCHROME c RELEASE.
F. Li, A. Srinivasan, Y. Wang, R. C. Armstrong, K. J. Tomaselli, and L. C. Fritz (1997)
J. Biol. Chem. 272, 30299-30305
   Abstract »    Full Text »    PDF »
Activation of distinct caspase-like proteases by Fas and reaper in Drosophila cells.
T. Kondo, T. Yokokura, and S. Nagata (1997)
PNAS 94, 11951-11956
   Abstract »    Full Text »    PDF »
Cross-Resistance of CD95- and Drug-Induced Apoptosis as a Consequence of Deficient Activation of Caspases (ICE/Ced-3 Proteases).
M. Los, I. Herr, C. Friesen, S. Fulda, K. Schulze-Osthoff, and K.-M. Debatin (1997)
Blood 90, 3118-3129
   Abstract »    Full Text »    PDF »
Inhibition of Reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs).
D. Vucic, W. J. Kaiser, A. J. Harvey, and L. K. Miller (1997)
PNAS 94, 10183-10188
   Abstract »    Full Text »    PDF »
Early Growth Response-1-dependent Apoptosis Is Mediated by p53.
P. Nair, S. Muthukkumar, S. F. Sells, S.-S. Han, V. P. Sukhatme, and V. M. Rangnekar (1997)
J. Biol. Chem. 272, 20131-20138
   Abstract »    Full Text »    PDF »
Cooperative functions of the reaper and head involution defective genes in the programmed cell death of Drosophila central nervous system midline cells.
L. Zhou, A. Schnitzler, J. Agapite, L. M. Schwartz, H. Steller, and J. R. Nambu (1997)
PNAS 94, 5131-5136
   Abstract »    Full Text »    PDF »
P element insertion-dependent gene activation in the Drosophila eye.
B. A. Hay, R. Maile, and G. M. Rubin (1997)
PNAS 94, 5195-5200
   Abstract »    Full Text »    PDF »
Use of Arsenic Trioxide (As2O3 ) in the Treatment of Acute Promyelocytic Leukemia (APL): I. As2O3 Exerts Dose-Dependent Dual Effects on APL Cells.
G.-Q. Chen, X.-G. Shi, W. Tang, S.-M. Xiong, J. Zhu, X. Cai, Z.-G. Han, J.-H. Ni, G.-Y. Shi, P.-M. Jia, et al. (1997)
Blood 89, 3345-3353
   Abstract »    Full Text »    PDF »
A Common Binding Site Mediates Heterodimerization and Homodimerization of Bcl-2 Family Members.
J.-L. Diaz, T. Oltersdorf, W. Horne, M. McConnell, G. Wilson, S. Weeks, T. Garcia, and L. C. Fritz (1997)
J. Biol. Chem. 272, 11350-11355
   Abstract »    Full Text »    PDF »
DCP-1, a Drosophila Cell Death Protease Essential for Development.
Z. Song, K. McCall, and H. Steller (1997)
Science 275, 536-540
   Abstract »    Full Text »
Steroid regulated programmed cell death during Drosophila metamorphosis.
C Jiang, E. Baehrecke, and C. Thummel (1997)
Development 124, 4673-4683
   Abstract »    PDF »
Identification of genes induced by factor deprivation in hematopoietic cells undergoing apoptosis using gene-trap mutagenesis and site-specific recombination.
A. P. Russ, C. Friedel, K. Ballas, U. Kalina, D. Zahn, K. Strebhardt, and H. von Melchner (1996)
PNAS 93, 15279-15284
   Abstract »    Full Text »    PDF »
Apoptotic Activity of REAPER Is Distinct from Signaling by the Tumor Necrosis Factor Receptor 1Death Domain.
P. Chen, P. Lee, L. Otto, and J. Abrams (1996)
J. Biol. Chem. 271, 25735-25737
   Abstract »    Full Text »    PDF »
grim, a novel cell death gene in Drosophila..
P Chen, W Nordstrom, B Gish, and J M Abrams (1996)
Genes & Dev. 10, 1773-1782
   Abstract »    PDF »
Neurotrophins and Their p75 Receptor.
B.D. Carter, G. Dechant, J.M. Frade, C. Kaltschmidt, and Y.-A. Barde (1996)
Cold Spring Harb Symp Quant Biol 61, 407-415
   Abstract »    PDF »
The Drosophila Caspase DRONC Cleaves following Glutamate or Aspartate and Is Regulated by DIAP1, HID, and GRIM.
C. J. Hawkins, S. J. Yoo, E. P. Peterson, S. L. Wang, S. Y. Vernooy, and B. A. Hay (2000)
J. Biol. Chem. 275, 27084-27093
   Abstract »    Full Text »    PDF »
An Essential Role for the Caspase Dronc in Developmentally Programmed Cell Death in Drosophila.
L. M. Quinn, L. Dorstyn, K. Mills, P. A. Colussi, P. Chen, M. Coombe, J. Abrams, S. Kumar, and H. Richardson (2000)
J. Biol. Chem. 275, 40416-40424
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)