Ubiquitylation in apoptosis: a post-translational modification at the edge of life and death (original) (raw)
Deshaies, R. J. & Joazeiro, C. A. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem.78, 399–434 (2009). CASPubMed Google Scholar
Pickart, C. M. Mechanisms underlying ubiquitination. Annu. Rev. Biochem.70, 503–533 (2001). CASPubMed Google Scholar
Deshaies, R. J. SCF and Cullin/Ring H2-based ubiquitin ligases. Annu. Rev. Cell Dev. Biol.15, 435–467 (1999). CASPubMed Google Scholar
Ikeda, F. & Dikic, I. Atypical ubiquitin chains: new molecular signals. 'Protein modifications: beyond the usual suspects' review series. EMBO Rep.9, 536–542 (2008). CASPubMedPubMed Central Google Scholar
Eddins, M. J., Carlile, C. M., Gomez, K. M., Pickart, C. M. & Wolberger, C. Mms2–Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. Nature Struct. Mol. Biol.13, 915–920 (2006). CAS Google Scholar
Rodrigo-Brenni, M. C., Foster, S. A. & Morgan, D. O. Catalysis of lysine 48-specific ubiquitin chain assembly by residues in E2 and ubiquitin. Mol. Cell39, 548–559 (2010). CASPubMedPubMed Central Google Scholar
Wickliffe, K. E., Lorenz, S., Wemmer, D. E., Kuriyan, J. & Rape, M. The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2. Cell144, 769–781 (2011). CASPubMedPubMed Central Google Scholar
Kirkin, V. & Dikic, I. Role of ubiquitin- and Ubl-binding proteins in cell signaling. Curr. Opin. Cell Biol.19, 199–205 (2007). CASPubMed Google Scholar
Finley, D., Ciechanover, A. & Varshavsky, A. Ubiquitin as a central cellular regulator. Cell116, S29–S32 (2004). CASPubMed Google Scholar
Salvesen, G. S. & Abrams, J. M. Caspase activation — stepping on the gas or releasing the brakes? Lessons from humans and flies. Oncogene23, 2774–2784 (2004). CASPubMed Google Scholar
Kaufmann, S. H. & Vaux, D. L. Alterations in the apoptotic machinery and their potential role in anticancer drug resistance. Oncogene22, 7414–7430 (2003). CASPubMed Google Scholar
Youle, R. J. & Strasser, A. The BCL-2 protein family: opposing activities that mediate cell death. Nature Rev. Mol. Cell Biol.9, 47–59 (2008). CAS Google Scholar
Du, C., Fang, M., Li, Y., Li, L. & Wang, X. Smac, a mitochondrial protein that promotes cytochrome _c_-dependent caspase activation by eliminating IAP inhibition. Cell102, 33–42 (2000). CASPubMed Google Scholar
Liu, X., Kim, C. N., Yang, J., Jemmerson, R. & Wang, X. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell86, 147–157 (1996). CASPubMed Google Scholar
Verhagen, A. M. et al. Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell102, 43–53 (2000). CASPubMed Google Scholar
Riedl, S. J. & Salvesen, G. S. The apoptosome: signalling platform of cell death. Nature Rev. Mol. Cell Biol.8, 405–413 (2007). CAS Google Scholar
Ashkenazi, A. & Dixit, V. M. Death receptors: signaling and modulation. Science281, 1305–1308 (1998). CASPubMed Google Scholar
Strasser, A., Jost, P. J. & Nagata, S. The many roles of FAS receptor signaling in the immune system. Immunity30, 180–192 (2009). CASPubMedPubMed Central Google Scholar
Tschopp, J., Irmler, M. & Thome, M. Inhibition of Fas death signals by FLIPs. Curr. Opin. Immunol.10, 552–558 (1998). CASPubMed Google Scholar
Salvesen, G. S. & Duckett, C. S. IAP proteins: blocking the road to death's door. Nature Rev. Mol. Cell Biol.3, 401–410 (2002). CAS Google Scholar
Vucic, D. et al. Engineering ML-IAP to produce an extraordinarily potent caspase 9 inhibitor: implications for Smac-dependent anti-apoptotic activity of ML-IAP. Biochem. J.385, 11–20 (2005). CASPubMed Google Scholar
Vousden, K. H. & Prives, C. Blinded by the light: the growing complexity of p53. Cell137, 413–431 (2009). CASPubMed Google Scholar
Huang, J., Plass, C. & Gerhäuser, C. Cancer chemoprevention by targeting the epigenome. Curr. Drug Targets. 15 Dec 2010 [epub ahead of print].
Declercq, W., Vanden Berghe, T. & Vandenabeele, P. RIP kinases at the crossroads of cell death and survival. Cell138, 229–232 (2009). CASPubMed Google Scholar
Wertz, I. E. & Dixit, V. M. Regulation of death receptor signaling by the ubiquitin system. Cell Death Differ.17, 14–24 (2010). CASPubMed Google Scholar
Zhang, H. G., Wang, J., Yang, X., Hsu, H. C. & Mountz, J. D. Regulation of apoptosis proteins in cancer cells by ubiquitin. Oncogene23, 2009–2015 (2004). CASPubMed Google Scholar
Steller, H. Regulation of apoptosis in Drosophila. Cell Death Differ.15, 1132–1138 (2008). CASPubMed Google Scholar
Sandu, C., Ryoo, H. D. & Steller, H. Drosophila IAP antagonists form multimeric complexes to promote cell death. J. Cell Biol.190, 1039–1052 (2010). CASPubMedPubMed Central Google Scholar
Koto, A., Kuranaga, E. & Miura, M. Temporal regulation of Drosophila IAP1 determines caspase functions in sensory organ development. J. Cell Biol.187, 219–231 (2009). CASPubMedPubMed Central Google Scholar
Broemer, M. et al. Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Mol. Cell40, 810–822 (2010). CASPubMed Google Scholar
Ditzel, M. et al. Inactivation of effector caspases through nondegradative polyubiquitylation. Mol. Cell32, 540–553 (2008). CASPubMedPubMed Central Google Scholar
Bader, M., Arama, E. & Steller, H. A novel F-box protein is required for caspase activation during cellular remodeling in Drosophila. Development137, 1679–1688 (2010). CASPubMedPubMed Central Google Scholar
Eckelman, B. P., Salvesen, G. S. & Scott, F. L. Human inhibitor of apoptosis proteins: why XIAP is the black sheep of the family. EMBO Rep.7, 988–994 (2006). CASPubMedPubMed Central Google Scholar
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. USA98, 8662–8667 (2001). CASPubMedPubMed Central Google Scholar
Schile, A. J., Garcia-Fernandez, M. & Steller, H. Regulation of apoptosis by XIAP ubiquitin-ligase activity. Genes Dev.22, 2256–2266 (2008). Demonstrates the importance of XIAP ubiquitin ligase activity for the regulation of apoptosis. CASPubMedPubMed Central Google Scholar
Choi, Y. E. et al. The E3 ubiquitin ligase c-IAP1 binds and ubiquitinates caspase-3 and -7 via unique mechanisms at distinct steps in their processing. J. Biol. Chem.284, 12772–12782 (2009). CASPubMedPubMed Central Google Scholar
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). CASPubMed Google Scholar
MacFarlane, M., Merrison, W., Bratton, S. B. & Cohen, G. M. Proteasome-mediated degradation of Smac during apoptosis: XIAP promotes Smac ubiquitination in vitro. J. Biol. Chem.277, 36611–36616 (2002). CASPubMed Google Scholar
Conze, D. B. et al. Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Mol. Cell. Biol.25, 3348–3356 (2005). CASPubMedPubMed Central Google Scholar
Silke, J. et al. Determination of cell survival by RING-mediated regulation of inhibitor of apoptosis (IAP) protein abundance. Proc. Natl Acad. Sci. USA102, 16182–16187 (2005). CASPubMedPubMed Central Google Scholar
Dogan, T. et al. X-linked and cellular IAPs modulate the stability of C-RAF kinase and cell motility. Nature Cell Biol.10, 1447–1455 (2008). CASPubMed Google Scholar
Xu, L. et al. c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Mol. Cell28, 914–922 (2007). CASPubMed Google Scholar
Li, X., Yang, Y. & Ashwell, J. D. TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature416, 345–347 (2002). PubMed Google Scholar
Micheau, O. & Tschopp, J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell114, 181–190 (2003). The first description of two distinct signalling complexes initiated by TNFR1 activation that differentially regulate apoptosis and are modulated by distinct ubiquitylation events. CASPubMed Google Scholar
Rothe, M., Pan, M. G., Henzel, W. J., Ayres, T. M. & Goeddel, D. V. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell83, 1243–1252 (1995). The authors identify c-IAP proteins in a TNFR-associated signalling complex. CASPubMed Google Scholar
Bertrand, M. J. et al. c-IAP1 and c-IAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell30, 689–700 (2008). CASPubMed Google Scholar
Dynek, J. N. et al. c-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J.29, 4198–4209 (2010). CASPubMedPubMed Central Google Scholar
Varfolomeev, E. et al. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor α (TNFα)-induced NF-κB activation. J. Biol. Chem.283, 24295–24299 (2008). References 47 and 49 identify c-IAP1 and c-IAP2 as ubiquitin ligases for RIP1. CASPubMedPubMed Central Google Scholar
Mahoney, D. J. et al. Both c-IAP1 and c-IAP2 regulate TNFα-mediated NF-κB activation. Proc. Natl Acad. Sci. USA105, 11778–11783 (2008). CASPubMedPubMed Central Google Scholar
Ikeda, F., Crosetto, N. & Dikic, I. What determines the specificity and outcomes of ubiquitin signaling? Cell143, 677–681 (2010). CASPubMed Google Scholar
Gerlach, B. et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature471, 591–596 (2011). CASPubMed Google Scholar
Xu, M., Skaug, B., Zeng, W. & Chen, Z. J. A ubiquitin replacement strategy in human cells reveals distinct mechanisms of IKK activation by TNFα and IL-1β. Mol. Cell36, 302–314 (2009). CASPubMedPubMed Central Google Scholar
Haas, T. L. et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol. Cell36, 831–844 (2009). CASPubMed Google Scholar
Tokunaga, F. et al. Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nature Cell Biol.11, 123–132 (2009). The first description of linear polyubiquitination in TNF signalling. CASPubMed Google Scholar
Ikeda, F. et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-κB activity and apoptosis. Nature471, 637–641 (2011). CASPubMedPubMed Central Google Scholar
Tokunaga, F. et al. SHARPIN is a component of the NF-κB-activating linear ubiquitin chain assembly complex. Nature471, 633–636 (2011). CASPubMed Google Scholar
Vallabhapurapu, S. et al. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-κB signaling. Nature Immunol.9, 1364–1370 (2008). CAS Google Scholar
Varfolomeev, E. et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-κB activation, and TNFα-dependent apoptosis. Cell131, 669–681 (2007). Provides evidence that IAP antagonists activate ubiquitin ligase activity of c-IAP proteins and identifies these proteins as crucial E3 ligases for NIK. CASPubMed Google Scholar
Vince, J. E. et al. IAP antagonists target c-IAP1 to induce TNFα-dependent apoptosis. Cell131, 682–693 (2007). Further evidence that IAP antagonists activate ubiquitin ligase activity of c-IAP proteins. CASPubMed Google Scholar
Zarnegar, B. J. et al. Noncanonical NF-κB activation requires coordinated assembly of a regulatory complex of the adaptors c-IAP1, c-IAP2, TRAF2 and TRAF3 and the kinase NIK. Nature Immunol.9, 1371–1378 (2008). CAS Google Scholar
Vince, J. E. et al. TWEAK-FN14 signaling induces lysosomal degradation of a c-IAP1-TRAF2 complex to sensitize tumor cells to TNFα. J. Cell Biol.182, 171–184 (2008). CASPubMedPubMed Central Google Scholar
Dejardin, E. The alternative NF-κB pathway from biochemistry to biology: pitfalls and promises for future drug development. Biochem. Pharmacol.72, 1161–1179 (2006). CASPubMed Google Scholar
Varfolomeev, E. & Vucic, D. (Un)expected roles of c-IAPs in apoptotic and NF-κB signaling pathways. Cell Cycle7, 1511–1521 (2008). CASPubMed Google Scholar
Matsuzawa, A. et al. Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex. Science321, 663–668 (2008). CASPubMedPubMed Central Google Scholar
Gardam, S. et al. Deletion of c-IAP1 and c-IAP2 in murine B lymphocytes constitutively activates cell survival pathways and inactivates the germinal center response. Blood117, 4041–4051 (2011). CASPubMed Google Scholar
Petersen, S. L. et al. Autocrine TNFα signaling renders human cancer cells susceptible to smac-mimetic-induced apoptosis. Cancer Cell12, 445–456 (2007). CASPubMedPubMed Central Google Scholar
Vandenabeele, P., Galluzzi, L., Vanden Berghe, T. & Kroemer, G. Molecular mechanisms of necroptosis: an ordered cellular explosion. Nature Rev. Mol. Cell Biol.11, 700–714 (2010). CAS Google Scholar
Conze, D. B., Zhao, Y. & Ashwell, J. D. Non-canonical NF-κB activation and abnormal B cell accumulation in mice expressing ubiquitin protein ligase-inactive c-IAP2. PLoS Biol.8, e1000518 (2010). PubMedPubMed Central Google Scholar
Zilfou, J. T. & Lowe, S. W. Tumor suppressive functions of p53. Cold Spring Harb. Perspect. Biol.1, a001883 (2009). PubMedPubMed Central Google Scholar
Jain, A. K. & Barton, M. C. Making sense of ubiquitin ligases that regulate p53. Cancer Biol. Ther.10, 665–672 (2010). CASPubMedPubMed Central Google Scholar
Wade, M., Wang, Y. V. & Wahl, G. M. The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol.20, 299–309 (2010). CASPubMedPubMed Central Google Scholar
Huang, H. & Tindall, D. J. Regulation of FOXO protein stability via ubiquitination and proteasome degradation. Biochim. Biophys. Acta 14 Jan 2011 (doi:10.1016/j.bbamcr.2011.01.007). CAS Google Scholar
Marine, J. C. & Lozano, G. Mdm2-mediated ubiquitylation: p53 and beyond. Cell Death Differ.17, 93–102 (2010). CASPubMed Google Scholar
Maguire, M. et al. MDM2 regulates dihydrofolate reductase activity through monoubiquitination. Cancer Res.68, 3232–3242 (2008). CASPubMedPubMed Central Google Scholar
Itahana, K. et al. Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell12, 355–366 (2007). CASPubMed Google Scholar
Inuzuka, H. et al. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCFβ-TRCP ubiquitin ligase. Cancer Cell18, 147–159 (2010). CASPubMedPubMed Central Google Scholar
Melino, G., Knight, R. A. & Cesareni, G. Degradation of p63 by Itch. Cell Cycle5, 1735–1739 (2006). CASPubMed Google Scholar
Chang, L. et al. The E3 ubiquitin ligase itch couples JNK activation to TNFα-induced cell death by inducing c-FLIPL turnover. Cell124, 601–613 (2006). CASPubMed Google Scholar
Winter, M. et al. Control of HIPK2 stability by ubiquitin ligase Siah-1 and checkpoint kinases ATM and ATR. Nature Cell Biol.10, 812–824 (2008). CASPubMed Google Scholar
Garrison, J. B. et al. ARTS and Siah collaborate in a pathway for XIAP degradation. Mol. Cell41, 107–116 (2011). CASPubMed Google Scholar
Gottfried, Y., Rotem, A., Lotan, R., Steller, H. & Larisch, S. The mitochondrial ARTS protein promotes apoptosis through targeting XIAP. EMBO J.23, 1627–1635 (2004). CASPubMedPubMed Central Google Scholar
Nakayama, K. & Ronai, Z. Siah: new players in the cellular response to hypoxia. Cell Cycle3, 1345–1347 (2004). CASPubMed Google Scholar
Kaelin, W. G. Proline hydroxylation and gene expression. Annu. Rev. Biochem.74, 115–128 (2005). CASPubMed Google Scholar
Skaar, J. R., D'Angiolella, V., Pagan, J. K. & Pagano, M. SnapShot: F box proteins II. Cell137, 1358.e1–1358.e2 (2009). Google Scholar
Frescas, D. & Pagano, M. Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer. Nature Rev. Cancer8, 438–449 (2008). CAS Google Scholar
Feinstein-Rotkopf, Y. & Arama, E. Can't live without them, can live with them: roles of caspases during vital cellular processes. Apoptosis14, 980–995 (2009). PubMed Google Scholar
Bai, C. et al. SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell86, 263–274, (1996). CASPubMed Google Scholar
Guardavaccaro, D. et al. Control of meiotic and mitotic progression by the F box protein β-Trcp1 in vivo. Dev. Cell4, 799–812 (2003). CASPubMed Google Scholar
Nakayama, K. et al. Impaired degradation of inhibitory subunit of NF-κB (IκB) and β-catenin as a result of targeted disruption of the β-TrCP1 gene. Proc. Natl Acad. Sci. USA100, 8752–8757 (2003). CASPubMedPubMed Central Google Scholar
Busino, L. et al. Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage. Nature426, 87–91 (2003). CASPubMed Google Scholar
Soldatenkov, V. A., Dritschilo, A., Ronai, Z. & Fuchs, S. Y. Inhibition of homologue of Slimb (HOS) function sensitizes human melanoma cells for apoptosis. Cancer Res.59, 5085–5088 (1999). CASPubMed Google Scholar
Dehan, E. et al. βTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Mol. Cell33, 109–116 (2009). CASPubMedPubMed Central Google Scholar
Tan, M. et al. SAG–ROC-SCFβ-TrCP E3 ubiquitin ligase promotes pro–caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia8, 1042–1054 (2006). CASPubMedPubMed Central Google Scholar
Gallegos, J. R. et al. SCFβTrCP1 activates and ubiquitylates TAp63γ. J. Biol. Chem.283, 66–75 (2008). CASPubMed Google Scholar
Xia, Y. et al. Phosphorylation of p53 by IκB kinase 2 promotes its degradation by β-TrCP. Proc. Natl Acad. Sci. USA106, 2629–2634 (2009). CASPubMedPubMed Central Google Scholar
Soond, S. M. et al. ERK and the F-box protein βTRCP target STAT1 for degradation. J. Biol. Chem.283, 16077–16083 (2008). CASPubMedPubMed Central Google Scholar
Dorrello, N. V. et al. S6K1- and βTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science314, 467–471 (2006). CASPubMed Google Scholar
Ding, Q. et al. Degradation of Mcl-1 by β-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol. Cell. Biol.27, 4006–4017 (2007). CASPubMed Google Scholar
Kanemori, Y., Uto, K. & Sagata, N. β-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. Proc. Natl Acad. Sci. USA102, 6279–6284 (2005). CASPubMedPubMed Central Google Scholar
Tetzlaff, M. T. et al. Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc. Natl Acad. Sci. USA101, 3338–3345 (2004). CASPubMedPubMed Central Google Scholar
Welcker, M. & Clurman, B. E. FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nature Rev. Cancer8, 83–93 (2008). CAS Google Scholar
Hoeck, J. D. et al. Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nature Neurosci.13, 1365–1372 (2010). CASPubMed Google Scholar
Crusio, K. M., King, B., Reavie, L. B. & Aifantis, I. The ubiquitous nature of cancer: the role of the SCFFbw7 complex in development and transformation. Oncogene29, 4865–4873 (2010). CASPubMedPubMed Central Google Scholar
Schwanbeck, R., Martini, S., Bernoth, K. & Just, U. The Notch signaling pathway: molecular basis of cell context dependency. Eur. J. Cell Biol.90, 572–581 (2010). PubMed Google Scholar
Mazumder, S., DuPree, E. L. & Almasan, A. A dual role of cyclin E in cell proliferation and apoptosis may provide a target for cancer therapy. Curr. Cancer Drug Targets4, 65–75 (2004). CASPubMedPubMed Central Google Scholar
Moberg, K. H., Mukherjee, A., Veraksa, A., Artavanis-Tsakonas, S. & Hariharan, I. K. The Drosophila F-box protein Archipelago regulates dMyc protein levels in vivo. Curr. Biol.14, 965–974 (2004). CASPubMed Google Scholar
Nateri, A. S., Riera-Sans, L., Da Costa, C. & Behrens, A. The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science303, 1374–1378 (2004). CASPubMed Google Scholar
Welcker, M. et al. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc. Natl Acad. Sci. USA101, 9085–9090 (2004). CASPubMedPubMed Central Google Scholar
Yada, M. et al. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J.23, 2116–2125 (2004). CASPubMedPubMed Central Google Scholar
Sánchez, I. & Yuan, J. A convoluted way to die. Neuron29, 563–566 (2001). PubMed Google Scholar
Inuzuka, H. et al. SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature471, 104–109 (2011). CASPubMedPubMed Central Google Scholar
Wertz, I. E. et al. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature471, 110–114 (2011). CASPubMed Google Scholar
Zhong, Q., Gao, W., Du, F. & Wang, X. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell121, 1085–1095 (2005). CASPubMed Google Scholar
Harley, M. E., Allan L. A., Sanderson H. S. & Clarke, P. R. Phosphorylation of Mcl-1 by CDK1–cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J.29, 2407–2420 (2010). CASPubMedPubMed Central Google Scholar
Wertz, I. E. & Dixit, V. M. Signaling to NF-κB: regulation by ubiquitination. Cold Spring Harb. Perspect. Biol.2, a003350 (2010). PubMedPubMed Central Google Scholar
Vaux, D. L. & Silke, J. IAPs, RINGs and ubiquitylation. Nature Rev. Mol. Cell Biol.6, 287–297 (2005). CAS Google Scholar
Bosanac, I. et al. Ubiquitin binding to A20 ZnF4 is required for modulation of NF-κB signaling. Mol. Cell40, 548–557 (2010). CASPubMed Google Scholar
Heyninck, K. & Beyaert, R. A20 inhibits NFκB activation by dual ubiquitin-editing functions. Trends Biochem. Sci.30, 1–4 (2005). CASPubMed Google Scholar
Wertz, I. E. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling. Nature430, 694–699 (2004). CASPubMed Google Scholar
Dixit, V. M. et al. Tumor necrosis factor-α induction of novel gene products in human endothelial cells including a macrophage-specific chemotaxin. J. Biol. Chem.265, 2973–2978 (1990). CASPubMed Google Scholar
Krikos, A., Laherty, C. D. & Dixit, V. M. Transcriptional activation of the tumor necrosis factor α-inducible zinc finger protein, A20, is mediated by κB elements. J. Biol. Chem.267, 17971–17976 (1992). CASPubMed Google Scholar
Hymowitz, S. G. & Wertz, I. E. A20: from ubiquitin editing to tumour suppression. Nature Rev. Cancer10, 332–341 (2010). CAS Google Scholar
Lee, E. G. et al. Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science289, 2350–2354 (2000). Reveals the critical importance of the A20 protein in regulating NF-κB signalling. CASPubMedPubMed Central Google Scholar
Verstrepen, L. et al. Expression, biological activities and mechanisms of action of A20 (TNFAIP3). Biochem. Pharmacol.80, 2009–2020 (2010). CASPubMed Google Scholar
Wertz, I. E. et al. Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase. Science303, 1371–1374 (2004). CASPubMed Google Scholar
Vereecke, L. et al. Enterocyte-specific A20 deficiency sensitizes to tumor necrosis factor-induced toxicity and experimental colitis. J. Exp. Med.207, 1513–1523 (2010). CASPubMedPubMed Central Google Scholar
Jin, Z. et al. Cullin3-based polyubiquitination and p62-dependent aggregation of caspase-8 mediate extrinsic apoptosis signaling. Cell137, 721–735 (2009). CASPubMed Google Scholar
Bignell, G. R. et al. Identification of the familial cylindromatosis tumour-suppressor gene. Nature Genet.25, 160–165 (2000). Describes the characterization of the CYLD tumour suppressor gene. CASPubMed Google Scholar
Saggar, S. et al. CYLD mutations in familial skin appendage tumours. J. Med. Genet.45, 298–302 (2008). CASPubMed Google Scholar
Sun, S. C. CYLD: a tumor suppressor deubiquitinase regulating NF-κB activation and diverse biological processes. Cell Death Differ.17, 25–34 (2010). CASPubMed Google Scholar
Kovalenko, A. et al. The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination. Nature424, 801–805 (2003). CASPubMed Google Scholar
Massoumi, R., Chmielarska, K., Hennecke, K., Pfeifer, A. & Fassler, R. Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-κB signaling. Cell125, 665–677 (2006). CASPubMed Google Scholar
Zhang, J. et al. Impaired regulation of NF-κB and increased susceptibility to colitis-associated tumorigenesis in CYLD-deficient mice. J. Clin. Invest.116, 3042–3049 (2006). CASPubMedPubMed Central Google Scholar
Wright, A. et al. Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD. Dev. Cell13, 705–716 (2007). CASPubMed Google Scholar
Wang, L., Du, F. & Wang, X. TNF-α induces two distinct caspase-8 activation pathways. Cell133, 693–703 (2008). CASPubMed Google Scholar
Vanlangenakker, N. et al. c-IAP1 and TAK1 protect cells from TNF-induced necrosis by preventing RIP1/RIP3-dependent reactive oxygen species production. Cell Death Differ.18, 656–665 (2011). CASPubMed Google Scholar
Lee, M. J., Lee, B. H., Hanna, J., King, R. W. & Finley, D. Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol. Cell Proteomics10, R110.003871 (2010). PubMedPubMed Central Google Scholar
Crimmins, S. et al. Transgenic rescue of ataxia mice reveals a male-specific sterility defect. Dev. Biol.325, 33–42 (2009). CASPubMed Google Scholar
Ehlers, M. D. Ubiquitin and synaptic dysfunction: ataxic mice highlight new common themes in neurological disease. Trends Neurosci.26, 4–7 (2003). CASPubMed Google Scholar
Crimmins, S. et al. Transgenic rescue of ataxia mice with neuronal-specific expression of ubiquitin-specific protease 14. J. Neurosci.26, 11423–11431 (2006). CASPubMedPubMed Central Google Scholar
Lee, B. H. et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature467, 179–184 (2010). The authors describe the development of a USP14 small molecule inhibitor to definitively demonstrate the role of USP14 in ubiquitin chain editing at the proteasome. CASPubMedPubMed Central Google Scholar
Shi, D. & Grossman, S. R. Ubiquitin becomes ubiquitous in cancer: emerging roles of ubiquitin ligases and deubiquitinases in tumorigenesis and as therapeutic targets. Cancer Biol. Ther.10, 737–747 (2010). CASPubMedPubMed Central Google Scholar
Pantaleon, M. et al. FAM deubiquitylating enzyme is essential for preimplantation mouse embryo development. Mech. Dev.109, 151–160 (2001). CASPubMed Google Scholar
Sacco, J. J., Coulson, J. M., Clague, M. J. & Urbe, S. Emerging roles of deubiquitinases in cancer-associated pathways. IUBMB life62, 140–157 (2010). CASPubMedPubMed Central Google Scholar
Jolly, L. A., Taylor, V. & Wood, S. A. USP9X enhances the polarity and self-renewal of embryonic stem cell-derived neural progenitors. Mol. Biol. Cell20, 2015–2029 (2009). CASPubMedPubMed Central Google Scholar
Schwickart, M. et al. Deubiquitinase USP9X stabilizes MCL1 and promotes tumour cell survival. Nature463, 103–107 (2010). CASPubMed Google Scholar
Nagai, H. et al. Ubiquitin-like sequence in ASK1 plays critical roles in the recognition and stabilization by USP9X and oxidative stress-induced cell death. Mol. Cell36, 805–818 (2009). CASPubMed Google Scholar
Everett, R. D. et al. A novel ubiquitin-specific protease is dynamically associated with the PML nuclear domain and binds to a herpesvirus regulatory protein. EMBO J.16, 1519–1530 (1997). CASPubMedPubMed Central Google Scholar
Faustrup, H., Bekker-Jensen, S., Bartek, J., Lukas, J. & Mailand, N. USP7 counteracts SCFβTrCP- but not APCCdh1-mediated proteolysis of Claspin. J. Cell Biol.184, 13–19 (2009). CASPubMedPubMed Central Google Scholar
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: the next generation. Cell144, 646–674 (2011). CASPubMed Google Scholar
Sureda, F. X. et al. Antiapoptotic drugs: a therapautic strategy for the prevention of neurodegenerative diseases. Curr. Pharm. Des.17, 230–245 (2011). CASPubMed Google Scholar
Dynek, J. N. et al. Microphthalmia-associated transcription factor is a critical transcriptional regulator of melanoma inhibitor of apoptosis in melanomas. Cancer Res.68, 3124–3132 (2008). CASPubMed Google Scholar
Hunter, A. M., LaCasse, E. C. & Korneluk, R. G. The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis12, 1543–1568 (2007). CASPubMed Google Scholar
Imoto, I. et al. Expression of c-IAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy. Cancer Res.62, 4860–4866 (2002). CASPubMed Google Scholar
Dierlamm, J. et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa- associated lymphoid tissue lymphomas. Blood93, 3601–3609 (1999). CASPubMed Google Scholar
Isaacson, P. G. Update on MALT lymphomas. Best Pract. Res. Clin. Haematol.18, 57–68 (2005). CASPubMed Google Scholar
Zhou, H., Du, M. Q. & Dixit, V. M. Constitutive NF-κB activation by the t(11;18)(q21;q21) product in MALT lymphoma is linked to deregulated ubiquitin ligase activity. Cancer Cell7, 425–431 (2005). CASPubMed Google Scholar
Ndubaku, C., Cohen, F., Varfolomeev, E. & Vucic, D. Targeting inhibitor of apoptosis (IAP) proteins for therapeutic intervention. Future Med. Chem.1, 1509–1525 (2009). CASPubMed Google Scholar
Sun, H. et al. Design, synthesis, and characterization of a potent, nonpeptide, cell-permeable, bivalent Smac mimetic that concurrently targets both the BIR2 and BIR3 domains in XIAP. J. Am. Chem. Soc.129, 15279–15294 (2007). CASPubMedPubMed Central Google Scholar
Vereecke, L., Beyaert, R. & van Loo, G. The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. Trends Immunol.30, 383–391 (2009). CASPubMed Google Scholar
Coornaert, B. et al. T cell antigen receptor stimulation induces MALT1 paracaspase-mediated cleavage of the NF-κB inhibitor A20. Nature Immunol.9, 263–271 (2008). CAS Google Scholar
Duwel, M. et al. A20 negatively regulates T cell receptor signaling to NF-κB by cleaving Malt1 ubiquitin chains. J. Immunol.182, 7718–7728 (2009). PubMed Google Scholar
Malynn, B. A. & Ma, A. A20 takes on tumors: tumor suppression by an ubiquitin-editing enzyme. J. Exp. Med.206, 977–980 (2009). CASPubMedPubMed Central Google Scholar
Dynek, J. N. & Vucic, D. Antagonists of IAP proteins as cancer therapeutics. Cancer Lett. 2 Aug 2010 (doi:10.1016/j.canlet.2010.06.013). CASPubMed Google Scholar
Baud, V. & Karin, M. Is NF-κB a good target for cancer therapy? Hopes and pitfalls. Nature Rev. Drug Discov.8, 33–40 (2009). CAS Google Scholar
Packham, G. The role of NF-κB in lymphoid malignancies. Br. J. Haematol.143, 3–15 (2008). CASPubMed Google Scholar
Baker, K. P. et al. Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator. Arthritis Rheum.48, 3253–3265 (2003). CASPubMed Google Scholar
Cummings, S. R. et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N. Engl. J. Med.361, 756–765 (2009). CASPubMed Google Scholar
Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res.68, 3421–3428 (2008). CASPubMed Google Scholar
Karin, M. The IκB kinase — a bridge between inflammation and cancer. Cell Res.18, 334–342 (2008). CASPubMed Google Scholar
Cheok, C. F., Verma, C. S., Baselga, J. & Lane, D. P. Translating p53 into the clinic. Nature Rev. Clin. Oncol.8, 25–37 (2011). CAS Google Scholar
Di Cintio, A., Di Gennaro, E. & Budillon, A. Restoring p53 function in cancer: novel therapeutic approaches for applying the brakes to tumorigenesis. Recent Pat. Anticancer Drug Discov.5, 1–13 (2010). CASPubMed Google Scholar
Mandinova, A. & Lee, S. W. The p53 pathway as a target in cancer therapeutics: obstacles and promise. Sci. Transl. Med.3, 64rv1 (2011). CASPubMedPubMed Central Google Scholar
Brown, C. J., Cheok, C. F., Verma, C. S. & Lane, D. P. Reactivation of p53: from peptides to small molecules. Trends Pharmacol. Sci.32, 53–62 (2011). CASPubMed Google Scholar
Vu, B. T. & Vassilev, L. Small-molecule inhibitors of the p53-MDM2 interaction. Curr. Top. Microbiol. Immunol.348, 151–172 (2011). CASPubMed Google Scholar
Colland, F. et al. Small-molecule inhibitor of USP7/HAUSP ubiquitin protease stabilizes and activates p53 in cells. Mol. Cancer Ther.8, 2286–2295 (2009). CASPubMed Google Scholar
Nicholson, B., Marblestone, J. G., Butt, T. R. & Mattern, M. R. Deubiquitinating enzymes as novel anticancer targets. Future Oncol.3, 191–199 (2007). CASPubMed Google Scholar
Adams, J. & Kauffman, M. Development of the proteasome inhibitor Velcade (bortezomib). Cancer Invest.22, 304–311 (2004). CASPubMed Google Scholar
McConkey, D. J. & Zhu, K. Mechanisms of proteasome inhibitor action and resistance in cancer. Drug Resist. Updat.11, 164–179 (2008). CASPubMed Google Scholar
Eldridge, A. G. & O'Brien, T. Therapeutic strategies within the ubiquitin proteasome system. Cell Death Differ.17, 4–13 (2010). CASPubMed Google Scholar
Grimm, S., Höhn, A. & Grune, T. Oxidative protein damage and the proteasome. Amino Acids 17 Jun 2010 (doi:10.1007/s00726-010-064620118).
Rodriguez-Gonzalez, A. et al. Targeting steroid hormone receptors for ubiquitination and degradation in breast and prostate cancer. Oncogene27, 7201–7211 (2008). CASPubMedPubMed Central Google Scholar
Lee, J. T. & Gu, W. The multiple levels of regulation by p53 ubiquitination. Cell Death Differ.17, 86–92 (2010). CASPubMed Google Scholar
Cummins, J. M. et al. Tumour suppression: disruption of HAUSP gene stabilizes p53. Nature 1 Apr 2004 (doi:10.1038/nature02501). Definitive evidence that the DUBHAUSPstabilizes p53 indirectly through MDM2 deubiquitylation. PubMed Google Scholar
Kon, N. et al. Inactivation of HAUSP in vivo modulates p53 function. Oncogene29, 1270–1279 (2010). CASPubMed Google Scholar
Kon, N. et al. Roles of HAUSP-mediated p53 regulation in central nervous system development. Cell Death Differ. 25 Feb 2011 (doi:10.1038/cdd.2011.12). CAS Google Scholar
Meulmeester, E., Pereg, Y., Shiloh, Y. & Jochemsen, A. G. ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle4, 1166–1170 (2005). CASPubMed Google Scholar