IAPs, RINGs and ubiquitylation

Nature Reviews Molecular Cell Biology

Volumn 6, Issue 4, 2005, Pages 287-297

  Vaux, David L ^a   Silke, John ^a  

^a WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

INHIBITOR OF APOPTOSIS PROTEIN; UBIQUITIN; UBIQUITIN CONJUGATING ENZYME;

AMINO ACID SEQUENCE; BACULOVIRUS; ENZYME ACTIVITY; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL; PROTEIN PROTEIN INTERACTION; REVIEW; UBIQUITINATION; ZINC FINGER MOTIF;

ANIMALS; CASPASES; HUMANS; INHIBITOR OF APOPTOSIS PROTEINS; PROTEIN STRUCTURE, TERTIARY; PROTEINS; TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED PEPTIDES AND PROTEINS; UBIQUITIN; UBIQUITIN-PROTEIN LIGASES;

INTRACISTERNAL A-PARTICLES; UNIDENTIFIED BACULOVIRUS;

EID: 17144377113     PISSN: 14710072     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrm1621     Document Type: Review

References (118)

1. Crook, N. E., Clem, R. J. & Miller, L. K. An apoptosis inhibiting baculovirus gene with a zinc finger-like motif. J. Mol. 67, 2168-2174 (1993).
2. Hinds, M. G., Norton, R. S., Vaux, D. L. & Day, C. L. Solution structure of a baculoviral inhibitor of apoptosis (IAP) repeat. Nature Struct. Biol. 6, 648-651 (1999).
3. Goyal, L. et al. Induction of apoptosis by Drosophila Reaper, Hid and Grim through inhibition of IAP function. EMBO J. 19, 589-597 (2000).
4. Lisi, S., Mazzon, I. & White, K. Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by Reaper and HID in Drosophila. Genetics 154, 669-678 (2000). References 3 and 4 provide the first evidence that the RING domain of an IAP is important in inhibiting cell death in vivo.
5. Joazeiro, C. A. et al. The tyrosine kinase negative regulator C-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science 286, 309-312 (1999).
6. Moynihan, T. P. et al. The ubiquitin-conjugating enzymes UbcH7 and UbcH8 interact with RING finger/IBR motif-containing domains of HHARI and H7-AP1. J. Biol. Chem. 274, 30963-30968 (1999).
7. Lorick, K. L. et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl Acad. Sci. USA 96, 11364-11369 (1999).
8. Silke, J. & Vaux, D. L. Two kinds of BIR-containing protein - inhibitors of apoptosis, or required for mitosis. J. Cell Sci. 114, 1821-1827 (2001).
9. Wang, S. L. et al. The Drosophila caspase inhibitor DIAP1 is essential for cell survival and is negatively regulated by HID. Cell 98, 453-463 (1999).
10. Zimmermann, K. C. et al. The role of ARK in stress-induced apoptosis in Drosophila cells. J. Cell Biol. 156, 1077-1087 (2002).
11. Igaki, T. et al. Downregulation of DIAP1 triggers a novel Drosophila cell death pathway mediated by Dark and DRONC. J. Biol. Chem. 277, 23103-23106 (2002).
12. Rodriguez, A. et al. Unrestrained caspase-dependent cell death caused by loss of Diap1 function requires the Drosophila Apaf-1 homolog, Dark. EMBO J. 21, 2189-2197 (2002).
13. Muro, I., Hay, B. A. & Clem, R. J. The Drosophila DIAP1 protein is required to prevent accumulation of a continuously generated, processed form of the apical caspase DRONC. J. Biol. Chem. 277, 49644-49650 (2002).
14. Hawkins, C. J., Wang, S. L. & Hay, B. A. A cloning method to identify caspases and their regulators in yeast: identification of Drosophila IAP1 as an inhibitor of the Drosophila caspase DCP-1. Proc. Natl Acad Sci. USA 96, 2885-2890 (1999).
15. Meier, P. et al. The Drosophila caspase DRONC is regulated by DIAP1. EMBO J. 19, 598-611 (2000).
16. Uren, A. G. et al. Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors. Proc. Natl Acad. Sci. USA 93, 4974-4978 (1996).
17. Duckett, C. S. et al. A conserved family of cellular genes related to the baculovirus IAP gene and encoding apoptosis inhibitors. EMBO J. 15, 2685-2694 (1996).
18. Deveraux, Q. L. et al. X-linked IAP is a direct inhibitor of cell-death proteases. Nature 388, 300-304 (1997). First description of an IAP as a caspase inhibitor.
19. Harlin, H. et al. Characterization of XIAP-deficient mice. Mol. Cell. Biol. 21, 3604-3608 (2001).
20. Salvesen, G. S. & Duckett, C. S. IAP proteins: blocking the road to death's door. Nature Rev. Mol. Cell Biol. 3, 401-410 (2002).
21. White, K. et al. Genetic control of programmed cell death in Drosophila. Science 264, 677-683 (1994).
22. Grether, M. E. et al. The head involution defective gene of Drosophila melanogaster functions in programmed cell death. Genes Dev. 9, 1694-1708 (1995).
23. Chen, P. et al. Grim, a novel cell death gene in Drosophila. Genes Dev. 10, 1773-1782 (1996).
24. Wing, J. P. et al. Drosophila sickle is a novel grim-reaper cell death activator. Curr. Biol. 12, 131-135 (2002).
25. Christich, A. et al. The damage-responsive Drosophila gene sickle encodes a novel IAP binding protein similar to but distinct from reaper, grim, and hid. Curr. Biol. 12, 137-140 (2002).
26. Srinivasula, S. M. et al. sickle, a novel Drosophila death gene in the reaper/hid/grim region, encodes an IAP-inhibitory protein. Curr. Biol. 12, 125-130 (2002).
27. Verhagen, A. M. et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102, 42-53 (2000).
28. Du, C. et al. Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102, 33-42 (2000). References 27 and 28 describe the identification of the first mammalian IAP antagonist.
29. Suzuki, Y. et al. A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol. Cell 8, 613-621 (2001).
30. Hegde, R. et al. Identification of Omi/HtrA2 as a mitochondrial apoptotic serine protease that disrupts inhibitor of apoptosis protein-caspase interaction. J. Biol. Chem. 277, 432-438 (2001).
31. Martins, L. M. et al. The serine protease Omi/HtrA2 regulates apoptosis by binding XIAP through a Reaper-like motif. J. Biol. Chem. 277, 439-444 (2001).
32. Verhagen, A. M. et al. HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J. Biol. Chem. 277, 445-454 (2001).
33. Hegde, R. et al. The polypeptide chain-releasing factor GSPT1/eRF3 is proteolytically processed into an IAP-binding protein. J. Biol. Chem. 278, 38699-38706 (2003).
34. Srinivasula, S. M. et al. A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis. Nature 410, 112-116 (2001). Describes a simple and elegant molecular mechanism of action for an IAP antagonist
35. Sun, C. et al. NMR structure and mutagenesis of the inhibitor-of- apoptosis protein XIAP. Nature 401, 818-821 (1999).
36. Silke, J. et al. Direct inhibition of caspase 3 is dispensable for the anti-apoptotic activity of XIAP. EMBO J. 20, 3114-3123 (2001).
37. Scott, F. L. et al. XIAP inhibits caspase-3 and-7 using two binding sites: evolutionary conserved mechanism of IAPs. EMBO J. 24, 645-655 (2005).
38. Pickart, C. M. Mechanisms underlying ubiquitination. Annu. Rev. Biochem. 70, 503-533 (2001).
39. Tyers, M. & Jorgensen, P. Proteolysis and the cell cycle: with this RING I do thee destroy. Curr. Opin. Genet. Dev. 10, 54-64 (2000).
40. Wing, J. P. et al. Drosophila Morgue is an F box/ubiquitin conjugase domain protein important for grim-reaper mediated apoptosis. Nature Cell Biol. 4, 451-456 (2002).
41. Hays, R., Wickline, L. & Cagan, R. Morgue mediates apoptosis in the Drosophila melanogaster retina by promoting degradation of DIAP1. Nature Cell Biol. 4, 425-431 (2002). References 40 and 41 describe the identification of Morgue, an F-box UEV that, when mutated, suppresses cell death induced by Reaper.
42. Hwang, W. W. et al. A conserved RING finger protein required for histone H2B mono-ubiquitination and cell size control. Mol. Cell 11, 261-266 (2003).
43. Wood, A. et al. Bre1, an E3 ubiquitin ligase required for recruitment and substrate selection of Rad6 at a promoter. Mol. Cell 11, 267-274 (2003).
44. Hochstrasser, M. Ubiquitin signalling: what's in a chain? Nature Cell Biol. 6, 571-572 (2004).
45. Koegl, M. et al. A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96, 635-644 (1999).
46. Aravind, L. & Koonin, E. V. The U box is a modified RING finger - a common domain in ubiquitination. Curr. Biol. 10, R132-R134 (2000).
47. Ohi, M. D. et al. Structural insights into the U-box, a domain associated with multi-ubiquitination. Nature Struct. Biol. 10, 250-255 (2003).
48. Hatakeyama, S. & Nakayama, K. I. U-box proteins as a new family of ubiquitin ligases. Biochem. Biophys. Res. Commun. 302, 635-645 (2003).
49. Andersen, P. et al. Structure and biochemical function of a prototypical Arabidopsis U-box domain. J. Biol. Chem. 279, 40053-40061 (2004).
50. Li, M. et al. Mono versus polyubiquitination: differential control of p53 fate by Mdm2. Science 302, 1972-1975 (2003).
51. Lai, Z. et al. Human mdm2 mediates multiple monoubiquitination of p53 by a mechanism requiring enzyme isomerization. J. Biol. Chem. 276, 31357-31367 (2001).
52. Wilson, R. et al. The DIAP1 RING finger mediates ubiquitination of Dronc and is indispensable for regulating apoptosis. Nature Cell Biol. 4, 445-450 (2002).
53. Yokokura, T. et al. Dissection of DIAP1 functional domains via a mutant replacement strategy. J. Biol. Chem. 279, 52603-52612 (2004).
54. Zachariou, A. et al. IAP-antagonists exhibit non-redundant modes of action through differential DIAP1 binding. EMBO J. 22, 6642-6652 (2003).
55. Yoo, S. J. et al. Hid, Rpr and Grim negatively regulate DIAP1 levels through distinct mechanisms. Nature Cell Biol. 4, 416-424 (2002).
56. Holley, C. L. et al. Reaper eliminates IAP proteins through stimulated IAP degradation and generalized translational inhibition. Nature Cell Biol. 4, 439-444 (2002).
57. Ryoo, H. D. et al. Regulation of Drosophila IAP1 degradation and apoptosis by reaper and ubcD1. Nature Cell Biol. 4, 432-438 (2002). Describes genetic interaction between an E2 and an IAP.
58. Hu, S. & Yang, X. Cellular inhibitor of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO. J. Biol. Chem. 278, 10055-10060 (2003).
59. Yang, Q. H. & Du, C. Smac/DIABLO selectively reduces the levels of C-IAP1 and C-IAP2 but not that of XIAP and livin in HeLa cells. J. Biol. Chem. 279, 16963-16970 (2004).
60. Qiu, X. B. & Goldberg, A. L. Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3. Proc. Natl Acad. Sci. USA 99, 14843-14848 (2002).
61. Kim, M. et al. Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent protein degradation. Oncogene 23, 1645-1655 (2004).
62. Brzovic, P. S. et al. Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex. Proc. Natl Acad. Sci. USA 100, 5646-5651 (2003).
63. Hashizume, R. et al. The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation. J. Biol. Chem. 276, 14537-14540 (2001).
64. Hofmann, R. M. & Pickart, C. M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96, 645-653 (1999).
65. Sancho, E. et al. Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29- M6 intestinal mucosecretory cells. Mol. Cell. Biol. 18, 576-589 (1998).
66. Wang, C. et al. TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412, 346-351 (2001).
67. Tenev, T. et al. Jafrac2 is an IAP antagonist that promotes cell death by liberating Drone from DIAP1. EMBO J. 21, 5118-5129 (2002).
68. Olson, M. R. et al. Reaper is regulated by IAP-mediated ubiquitination. J. Biol. Chem. 278, 4028-4034 (2003).
69. Bachmair, A., Finley, D. & Varshavsky, A. In vivo half-life of a protein is a function of its amino-terminal residue. Science 234, 179-186 (1986).
70. Hunter, A. M. et al. A novel ubiquitin fusion system bypasses the mitochondria and generates biologically active Smac/DIABLO. J. Biol. Chem. 278, 7494-7499 (2003).
71. MacFarlane, M. et al. Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J. Biol. Chem. 277, 36611-36616 (2002).
72. Wilkinson, J. C. et al. Neutralization of Smac/Diablo by inhibitors of apoptosis (IAPs): a caspase-independent mechanism for apoptotic inhibition. J. Biol. Chem. 279, 51082-51090 (2004).
73. Silke, J. et al. Unlike Diablo/smac, Grim promotes global ubiquitination and specific degradation of XIAP and neither cause apoptosis. J. Biol. Chem. 279, 4313-4321 (2004).
74. Creagh, E. M. et al. Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins. J. Biol. Chem. 279, 26906-26914 (2004).
75. Bartke, T. et al. Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol. Cell 14, 801-811 (2004).
76. Hao, Y. et al. Apollon ubiquitinates SMAC and caspase-9, and has an essential cytoprotection function. Nature Cell Biol. 6, 849-860 (2004).
77. Vernooy, S. Y. et al. Drosophila Bruce can potently suppress Rpr- and Grim-dependent but not Hid-dependent cell death. Curr. Biol. 12, 1164-1168 (2002).
78. Fu, J., Jin, Y. & Arend, L. J. Smac3, a novel Smac/DIABLO splicing variant, attenuates the stability and apoptosis-inhibiting activity of X-linked inhibitor of apoptosis protein. J. Biol. Chem. 278, 52660-52672 (2003).
79. Ditzel, M. & Meier, P. IAP degradation: decisive blow or altruistic sacrifice? Trends Cell Biol. 12, 449-452 (2002).
80. Hell, K. et al. Substrate cleavage by caspases generates protein fragments with Smac/Diablo-like activities. Cell Death Differ. 10, 1234-1239 (2003).
81. Vaux, D. L. & Silke, J. HtrA2/Omi, a sheep in wolf's clothing. Cell 115, 251-253 (2003).
82. Chai, J. et al. Molecular mechanism of Reaper-Grim-Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nature Struct Biol. 10, 892-898 (2003).
83. Yan, N. et al. Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid and Grim, Nature Struct. Mol. Biol. 11, 420-428 (2004).
84. Ryoo, H. D., Gorenc, T. & Steller, H. Apoptotic cells can induce compensatory cell proliferation through the JNK and the Wingless signaling pathways. Dev. Cell 7, 491-501 (2004).
85. Huang, H. et al. The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro mono-ubiquitination of caspases 3 and 7. J. Biol. Chem. 275, 26661-26664 (2000).
86. Suzuki, Y., Nakabayashi, Y. & Takahashi, R. Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death. Proc Natl Acad. Sci. USA 98, 8662-8667 (2001).
87. van De Sluis, B. et al. Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum. Mol. Genet. 11, 165-173 (2002).
88. Tao, T. Y. et al. The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. J. Biol. Chem. 278, 41593-41596 (2003).
89. Rothe, M. et al. The TNF-R2-TRAF signaling complex contains two novel proteins related to baculoviral-inhibitor of apoptosis proteins. Cell 83, 1243-1252 (1995).
90. Burstein, E. et al. A novel role for XIAP in copper homeostasis through regulation of MURR1. EMBO J. 23, 244-254 (2004).
91. Lee, S. Y. et al. Traf2 is essential for JNK but not NF-κB activation and regulates lymphocyte proliferation and survival. Immunity 7, 703-713 (1997).
92. Yeh, W. C. et al. Early lethality, functional NF-κB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity 7, 715-725 (1997).
93. Grech, A. P. et al. TRAF2 differentially regulates the canonical and noncanonical pathways of NF-κB activation in mature B cells. Immunity 21, 629-642 (2004).
94. Duckett, C. S. & Thompson, C. B. Cd30-dependent degradation of TRAF2-implications for negative regulation of TRAF signaling and the control of cell survival. Genes Dev. 11, 2810-2821 (1997).
95. Brown, K. D., Hostager, B. S. & Bishop, G. A. Regulation of TRAF2 signaling by self-induced degradation. J. Biol Chem. 277, 19433-19438 (2002).
96. Fotin-Mleczek, M. et al. Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8. J. Cell. Sci. 115, 2757-2770 (2002).
97. Li, X., Yang, Y. & Ashwell, J. D. TNF-RII and C-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 416, 345-347 (2002).
98. Kuranaga, E. et al. Reaper-mediated inhibition of DIAP1-induced DTRAF1 degradation results in activation of JNK in Drosophila. Nature Cell Biol. 4, 705-710 (2002).
99. Legler, D. F. et al. Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation. Immunity 18, 655-664 (2003).
100. Park, S. M., Yoon, J. B. & Lee, T. H. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (C-IAP1 and c-IAP2) in vitro. FEBS Lett. 566, 151-156 (2004).
101. Micheau, O. & Tschopp, J. Induction of TNF receptor 1-mediated apoptosis via two sequential signaling complexes. Cell 114, 181-190 (2003).
102. Lee, J. S. et al. Mass spectrometric analysis of tumor necrosis factor receptor-associated factor 1 ubiquitination mediated by cellular inhibitor of apoptosis 2. Proteomics 4, 3376-3382 (2004).
103. Devin, A. et al. The α and β subunits of IκB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF. Mol. Cell. Biol. 21, 3986-3994 (2001).
104. Tang, E. D. et al. A role for NF-κB essential modifier/IκB kinase-γ (NEMO/IKKγ) ubiquitination in the activation of the IκB kinase complex by tumor necrosis factor-α. J. Biol. Chem. 278, 37297-37305 (2003).
105. Silke, J. et al. The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3- and caspase 9-interacting sites. J. Cell Biol. 157, 115-124 (2002).
106. Yang, Y. et al. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 288, 874-877 (2000). First description of the ability of IAPs to function as E3 ligases and their selective loss following certain apoptotic signals.
107. Fang, S. et al. Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J. Biol. Chem. 275, 8945-8951 (2000).
108. Nuber, U., Schwarz, S. E. & Scheffner, M. The ubiquitin-protein ligase E6-associated protein (E6-AP) serves as its own substrate. Eur. J. Biochem. 254, 643-649 (1998).
109. Logan, I. R. et al. Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome. J. Biol. Chem. 279, 11696-11704 (2004).
110. Grossman, S. R. et al. Polyubiquitination of p53 by a ubiquitin ligase activity of p300. Science 300, 342-344 (2003).
111. Xirodimas, D. P. et al. Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 118, 83-97 (2004).
112. Linares, L. K. et al. HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53. Proc. Natl Acad. Sci. USA 100, 12009-12014 (2003).
113. de Graaf, P. et al. Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2. J. Biol. Chem. 278, 38315-38324 (2003).
114. Dornan, D. et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 429, 86-92 (2004).
115. Leng, R. P. et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 112, 779-791 (2003).
116. Shiozaki, E. N. & Shi, Y. Caspases, IAPs and Smac/DIABLO: mechanisms from structural biology. Trends Biochem. Sci. 29, 486-494 (2004).
117. Woo, M. et al. In vivo evidence that caspase-3 is required for Fas-mediate apoptosis of hepatocytes. J. Immun. 163, 4909-4916 (1999).
118. Skp2 SCF ubiquitin ligase complex. Nature 416, 703-709 (2002).