TY - JOUR
T1 - Bifunctional killing activity encoded by conserved reaper proteins
AU - Chen, P.
AU - Ho, S. I.
AU - Shi, Z.
AU - Abrams, John M.
N1 - Funding Information:
We would like to thank Dr. Yasuo Kitagawa for anti-dTFAM, Drs. Kristin White and Pascal Meier for anti-DIAP1 and Dr. Phil Batterham for the blowfly cDNA library. We thank Joe Chapo and Alex Caraveo for excellent technical support. This work was supported by grant AG12466 from the National Institute of Health to JMA. PC is a Leukemia and Lymphoma Society special fellow.
PY - 2004/7
Y1 - 2004/7
N2 - Drosophila activators of apoptosis mapping to the Reaper region function, in part, by antagonizing IAP proteins through a shared RHG motif. We isolated Reaper from the Blowfly L. cuprina, which triggered extensive apoptosis in Drosophila cells. Conserved regions of Reaper were tested in the context of GFP fusions and a second killing activity, distinct from the RHG, was identified. A 20 amino-acid peptide, designated R3, conferred targeting to a focal compartment and promoted membrane blebbing. Killing by the R3 fragment did not correlate with translational suppression or with reduced DIAP1 levels. Likewise, R3-induced cell deaths were only modestly suppressed by silencing of Dronc and involved no detectable association with DIAP1. Instead, a second IAP-binding domain, distinct from the R3, was identified at the C terminus of Reaper that bound to DIAP1 but failed to trigger apoptosis. Collectively, these findings are inconsistent with single effector models for cell killing by Reaper and suggest, instead, that Reaper encodes conserved bifunctional death activities that propagate through distinct effector pathways.
AB - Drosophila activators of apoptosis mapping to the Reaper region function, in part, by antagonizing IAP proteins through a shared RHG motif. We isolated Reaper from the Blowfly L. cuprina, which triggered extensive apoptosis in Drosophila cells. Conserved regions of Reaper were tested in the context of GFP fusions and a second killing activity, distinct from the RHG, was identified. A 20 amino-acid peptide, designated R3, conferred targeting to a focal compartment and promoted membrane blebbing. Killing by the R3 fragment did not correlate with translational suppression or with reduced DIAP1 levels. Likewise, R3-induced cell deaths were only modestly suppressed by silencing of Dronc and involved no detectable association with DIAP1. Instead, a second IAP-binding domain, distinct from the R3, was identified at the C terminus of Reaper that bound to DIAP1 but failed to trigger apoptosis. Collectively, these findings are inconsistent with single effector models for cell killing by Reaper and suggest, instead, that Reaper encodes conserved bifunctional death activities that propagate through distinct effector pathways.
KW - Apoptosis
KW - Caspases
KW - Drosophila
KW - IAP
KW - Reaper
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U2 - 10.1038/sj.cdd.4401406
DO - 10.1038/sj.cdd.4401406
M3 - Article
C2 - 15002042
AN - SCOPUS:3543132943
SN - 1350-9047
VL - 11
SP - 704
EP - 713
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 7
ER -