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Nat Cell Biol
2002 Jun 01;46:439-44. doi: 10.1038/ncb798.
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Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition.
Holley CL
,
Olson MR
,
Colón-Ramos DA
,
Kornbluth S
.
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Inhibitors of apoptosis (IAPs) inhibit caspases, thereby preventing proteolysis of apoptotic substrates. IAPs occlude the active sites of caspases to which they are bound and can function as ubiquitin ligases. IAPs are also reported to ubiquitinate themselves and caspases. Several proteins induce apoptosis, at least in part, by binding and inhibiting IAPs. Among these are the Drosophila melanogaster proteins Reaper (Rpr), Grim, and HID, and the mammalian proteins Smac/Diablo and Omi/HtrA2, all of which share a conserved amino-terminal IAP-binding motif. We report here that Rpr not only inhibits IAP function, but also greatly decreases IAP abundance. This decrease in IAP levels results from a combination of increased IAP degradation and a previously unrecognized ability of Rpr to repress total protein translation. Rpr-stimulated IAP degradation required both IAP ubiquitin ligase activity and an unblocked Rpr N terminus. In contrast, Rpr lacking a free N terminus still inhibited protein translation. As the abundance of short-lived proteins are severely affected after translational inhibition, the coordinated dampening of protein synthesis and the ubiquitin-mediated destruction of IAPs can effectively reduce IAP levels to lower the threshold for apoptosis.
Avdonin,
Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels.
1998, Pubmed,
Xenbase
Avdonin,
Apoptotic proteins Reaper and Grim induce stable inactivation in voltage-gated K+ channels.
1998,
Pubmed
,
Xenbase
Chai,
Structural basis of caspase-7 inhibition by XIAP.
2001,
Pubmed
Chen,
grim, a novel cell death gene in Drosophila.
1996,
Pubmed
Clem,
c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment.
2001,
Pubmed
Deveraux,
Cleavage of human inhibitor of apoptosis protein XIAP results in fragments with distinct specificities for caspases.
1999,
Pubmed
Evans,
Reaper-induced apoptosis in a vertebrate system.
1997,
Pubmed
,
Xenbase
Glotzer,
Cyclin is degraded by the ubiquitin pathway.
1991,
Pubmed
,
Xenbase
Goyal,
Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function.
2000,
Pubmed
Grether,
The head involution defective gene of Drosophila melanogaster functions in programmed cell death.
1995,
Pubmed
Hays,
Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1.
2002,
Pubmed
Huang,
The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7.
2000,
Pubmed
Huang,
Structural basis of caspase inhibition by XIAP: differential roles of the linker versus the BIR domain.
2001,
Pubmed
Martins,
The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a reaper-like motif.
2002,
Pubmed
Newmeyer,
Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria.
1994,
Pubmed
,
Xenbase
Richter,
The IAP proteins: caspase inhibitors and beyond.
2000,
Pubmed
Riedl,
Structural basis for the inhibition of caspase-3 by XIAP.
2001,
Pubmed
Suzuki,
A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.
2001,
Pubmed
Swenson,
Formation of gap junctions by expression of connexins in Xenopus oocyte pairs.
1989,
Pubmed
,
Xenbase
Verhagen,
Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins.
2000,
Pubmed
White,
Genetic control of programmed cell death in Drosophila.
1994,
Pubmed
Wu,
Structural analysis of a functional DIAP1 fragment bound to grim and hid peptides.
2001,
Pubmed
Wu,
Structural basis of IAP recognition by Smac/DIABLO.
,
Pubmed
Yang,
Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli.
2000,
Pubmed
