TY - JOUR
T1 - Dredd, a novel effector of the apoptosis activators Reaper, Grim, and Hid in Drosophila
AU - Chen, Po
AU - Rodriguez, Antony
AU - Erskine, Robert
AU - Thach, Tien
AU - Abrams, John M.
N1 - Funding Information:
We thank J. Chapo and S. I. Ho for help with the construction of expression vectors. We are also grateful to members of the Abrams lab for comments on drafts of the manuscript. We also thank J. R. Nambu for generously providing us with the P[UAS-rpr], P[UAS-grim], and P[UAS-hid] strains; K. White for providing P[GMR-rpr] flies; and G. Lawton for help with scanning electron microscopy. We also thank K. Matthews at the Bloomington stock center for GAL4 strains and finally D. McKearin for the ovary in situ protocol. This work was supported by grants from the American Cancer Society (CB-80362) and from NIH (AG12466) to J.M.A. T.T. was supported in part by an ARP from the Texas Higher Education Coordinating Board. P.C. is supported by a postdoctoral fellowship from NIH (GM18215-02).
PY - 1998/9/15
Y1 - 1998/9/15
N2 - Caspases are widely conserved proteases considered to be essential effectors of apoptosis. We identified a novel Drosophila gene, dredd, which shares extensive homology to all members of the caspase gene family. Cells specified for programmed death in development exhibit a striking accumulation of dredd RNA that requires signaling by the death activators REAPER, GRIM, and HID. Furthermore, directed misexpression of each activator was sufficient to drive ectopic accumulation of dredd RNA. Heterozygosity at the dredd locus suppressed apoptosis in transgenic models of reaper- and grim-induced cell killing, demonstrating that levels of dredd product can modulate signaling triggered by these death activators. Finally, expression of REAPER, GRIM, and HID was found to trigger processing of DREDD protein precursor through a mechanism that is insensitive to, and upstream of, known caspase inhibitors. Taken together, these observations establish mechanistic connections between activators of apoptosis and a new downstream death effector in Drosophila.
AB - Caspases are widely conserved proteases considered to be essential effectors of apoptosis. We identified a novel Drosophila gene, dredd, which shares extensive homology to all members of the caspase gene family. Cells specified for programmed death in development exhibit a striking accumulation of dredd RNA that requires signaling by the death activators REAPER, GRIM, and HID. Furthermore, directed misexpression of each activator was sufficient to drive ectopic accumulation of dredd RNA. Heterozygosity at the dredd locus suppressed apoptosis in transgenic models of reaper- and grim-induced cell killing, demonstrating that levels of dredd product can modulate signaling triggered by these death activators. Finally, expression of REAPER, GRIM, and HID was found to trigger processing of DREDD protein precursor through a mechanism that is insensitive to, and upstream of, known caspase inhibitors. Taken together, these observations establish mechanistic connections between activators of apoptosis and a new downstream death effector in Drosophila.
KW - Apoptosis
KW - Caspase
KW - Drosophila
KW - Programmed cell death
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U2 - 10.1006/dbio.1998.9000
DO - 10.1006/dbio.1998.9000
M3 - Article
C2 - 9740659
AN - SCOPUS:0032530359
SN - 0012-1606
VL - 201
SP - 202
EP - 216
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -