| Structural highlights
Function
[IAP1_DROME] Anti-apoptotic protein which functions as a caspase regulator, using its E3 ubiquitin-protein ligase activity to smother caspase activity. Binds, ubiquitinates and inactivates initiator caspase Nc, and effector caspases ICE and DCP-1. Acts as a NEDD8-E3 ubiquitin-protein ligase for ICE. Suppresses apoptosis by targeting the apoptosome for ubiquitination and inactivation. Plays an important role in cell motility. Overexpression suppresses rpr and W-dependent cell death in the eye. Interaction of th with Nc is required to suppress Nc-mediated cell death; th-mediated ubiquitination of Nc. Acts as a positive regulator of Wnt signaling.[1] [2] [3] [4] [5] [6] [ICENC_DROME] Involved in the activation cascade of caspases responsible for apoptosis execution. Effector of steroid-mediated apoptosis during insect metamorphosis. Overexpression promotes programmed cell death. Interaction with th is required to suppress Nc-mediated cell death; via th-mediated ubiquitination of Nc. Rate-limiting caspase in rpr and W death pathway.[7] [8] [9] [10]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The inhibitor of apoptosis protein DIAP1 inhibits Dronc-dependent cell death by ubiquitinating Dronc. The pro-death proteins Reaper, Hid and Grim (RHG) promote apoptosis by antagonizing DIAP1 function. Here we report the structural basis of Dronc recognition by DIAP1 as well as a novel mechanism by which the RHG proteins remove DIAP1-mediated downregulation of Dronc. Biochemical and structural analyses revealed that the second BIR (BIR2) domain of DIAP1 recognizes a 12-residue sequence in Dronc. This recognition is essential for DIAP1 binding to Dronc, and for targeting Dronc for ubiquitination. Notably, the Dronc-binding surface on BIR2 coincides with that required for binding to the N termini of the RHG proteins, which competitively eliminate DIAP1-mediated ubiquitination of Dronc. These observations reveal the molecular mechanisms of how DIAP1 recognizes Dronc, and more importantly, how the RHG proteins remove DIAP1-mediated ubiquitination of Dronc.
Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination.,Chai J, Yan N, Huh JR, Wu JW, Li W, Hay BA, Shi Y Nat Struct Biol. 2003 Nov;10(11):892-8. Epub 2003 Sep 28. PMID:14517550[11]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hay BA, Wassarman DA, Rubin GM. Drosophila homologs of baculovirus inhibitor of apoptosis proteins function to block cell death. Cell. 1995 Dec 29;83(7):1253-62. PMID:8548811
- ↑ Igaki T, Suzuki Y, Tokushige N, Aonuma H, Takahashi R, Miura M. Evolution of mitochondrial cell death pathway: Proapoptotic role of HtrA2/Omi in Drosophila. Biochem Biophys Res Commun. 2007 May 18;356(4):993-7. Epub 2007 Mar 26. PMID:17397804 doi:10.1016/j.bbrc.2007.03.079
- ↑ Khan FS, Fujioka M, Datta P, Fernandes-Alnemri T, Jaynes JB, Alnemri ES. The interaction of DIAP1 with dOmi/HtrA2 regulates cell death in Drosophila. Cell Death Differ. 2008 Jun;15(6):1073-83. doi: 10.1038/cdd.2008.19. Epub 2008, Feb 15. PMID:18259196 doi:10.1038/cdd.2008.19
- ↑ Broemer M, Tenev T, Rigbolt KT, Hempel S, Blagoev B, Silke J, Ditzel M, Meier P. Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Mol Cell. 2010 Dec 10;40(5):810-22. doi: 10.1016/j.molcel.2010.11.011. PMID:21145488 doi:10.1016/j.molcel.2010.11.011
- ↑ Hanson AJ, Wallace HA, Freeman TJ, Beauchamp RD, Lee LA, Lee E. XIAP monoubiquitylates Groucho/TLE to promote canonical Wnt signaling. Mol Cell. 2012 Mar 9;45(5):619-28. doi: 10.1016/j.molcel.2011.12.032. Epub 2012, Feb 1. PMID:22304967 doi:10.1016/j.molcel.2011.12.032
- ↑ Chai J, Yan N, Huh JR, Wu JW, Li W, Hay BA, Shi Y. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Biol. 2003 Nov;10(11):892-8. Epub 2003 Sep 28. PMID:14517550 doi:10.1038/nsb989
- ↑ Dorstyn L, Colussi PA, Quinn LM, Richardson H, Kumar S. DRONC, an ecdysone-inducible Drosophila caspase. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4307-12. PMID:10200258
- ↑ Meier P, Silke J, Leevers SJ, Evan GI. The Drosophila caspase DRONC is regulated by DIAP1. EMBO J. 2000 Feb 15;19(4):598-611. PMID:10675329 doi:http://dx.doi.org/10.1093/emboj/19.4.598
- ↑ Quinn LM, Dorstyn L, Mills K, Colussi PA, Chen P, Coombe M, Abrams J, Kumar S, Richardson H. An essential role for the caspase dronc in developmentally programmed cell death in Drosophila. J Biol Chem. 2000 Dec 22;275(51):40416-24. PMID:10984473 doi:http://dx.doi.org/10.1074/jbc.M002935200
- ↑ Chai J, Yan N, Huh JR, Wu JW, Li W, Hay BA, Shi Y. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Biol. 2003 Nov;10(11):892-8. Epub 2003 Sep 28. PMID:14517550 doi:10.1038/nsb989
- ↑ Chai J, Yan N, Huh JR, Wu JW, Li W, Hay BA, Shi Y. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nat Struct Biol. 2003 Nov;10(11):892-8. Epub 2003 Sep 28. PMID:14517550 doi:10.1038/nsb989
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