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Viral avoidance and exploitation of the ubiquitin system

Abstract

The versatility of ubiquitin in regulating protein function and cell behaviour through post-translational protein modification makes it a particularly attractive target for viruses. Here we review how viruses manipulate the ubiquitin system to favour their propagation by redirecting cellular ubiquitin enzymes or encoding their own ubiquitin components to enable replication, egress and immune evasion. These studies not only reveal the many cellular processes requiring ubiquitin but also illustrate how viruses usurp their host cells.

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Figure 1: The biochemistry of ubiquitin chain formation and de-ubiquitylation.
Figure 2: Avoidance and exploitation of ubiquitylation by viruses.
Figure 3: Viral manipulation of the ubiquitin system promotes degradation of cellular immunoreceptors.

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References

  1. Pickart, C. M. Back to the future with ubiquitin. Cell 116, 181–190 (2004).

    CAS  PubMed  Google Scholar 

  2. Mukhopadhyay, D. & Riezman, H. Proteasome-independent functions of ubiquitin in endocytosis and signaling. Science 315, 201–205 (2007).

    CAS  PubMed  Google Scholar 

  3. Reilly, L. M. & Guarino, L. A. The viral ubiquitin gene of Autographa californica nuclear polyhedrosis virus is not essential for viral replication. Virology 218, 243–247 (1996).

    CAS  PubMed  Google Scholar 

  4. Haas, A. L., Katzung, D. J., Reback, P. M. & Guarino, L. A. Functional characterization of the ubiquitin variant encoded by the baculovirus Autographa californica. Biochemistry 35, 5385–5394 (1996).

    CAS  PubMed  Google Scholar 

  5. Guarino, L. A., Smith, G. & Dong, W. Ubiquitin is attached to membranes of baculovirus particles by a novel type of phospholipid anchor. Cell 80, 301–309 (1995).

    CAS  PubMed  Google Scholar 

  6. Webb, J. H., Mayer, R. J. & Dixon, L. K. A lipid modified ubiquitin is packaged into particles of several enveloped viruses. FEBS Lett. 444, 136–139 (1999).

    CAS  PubMed  Google Scholar 

  7. Ichimura, Y. et al. A ubiquitin-like system mediates protein lipidation. Nature 408, 488–492 (2000).

    CAS  PubMed  Google Scholar 

  8. Becher, P., Thiel, H. J., Collins, M., Brownlie, J. & Orlich, M. Cellular sequences in pestivirus genomes encoding γ-aminobutyric acid (A) receptor-associated protein and Golgi-associated ATPase enhancer of 16 kilodaltons. J. Virol. 76, 13069–13076 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Yu, Y., Wang, S. E. & Hayward, G. S. The KSHV immediate-early transcription factor RTA encodes ubiquitin E3 ligase activity that targets IRF7 for proteosome-mediated degradation. Immunity 22, 59–70 (2005).

    CAS  PubMed  Google Scholar 

  10. Wang, X., Herr, R. A. & Hansen, T. Viral and cellular MARCH ubiquitin ligases and cancer. Semin. Cancer Biol. 18, 441–450 (2008).

    PubMed  PubMed Central  Google Scholar 

  11. Lehner, P. J., Hoer, S., Dodd, R. & Duncan, L. M. Downregulation of cell surface receptors by the K3 family of viral and cellular ubiquitin E3 ligases. Immunol. Rev. 207, 112–125 (2005).

    CAS  PubMed  Google Scholar 

  12. Boutell, C., Sadis, S. & Everett, R. D. Herpes simplex virus type 1 immediate-early protein ICP0 and its isolated RING finger domain act as ubiquitin E3 ligases in vitro. J. Virol. 76, 841–850 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Hagglund, R. & Roizman, B. Role of ICP0 in the strategy of conquest of the host cell by herpes simplex virus 1. J. Virol. 78, 2169–2178 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Everett, R. D. ICP0, a regulator of herpes simplex virus during lytic and latent infection. Bioessays 22, 761–770 (2000).

    CAS  PubMed  Google Scholar 

  15. Parkinson, J. & Everett, R. D. α-Herpesvirus proteins related to herpes simplex virus type 1 ICP0 affect cellular structures and proteins. J. Virol. 74, 10006–10017 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Hagglund, R. & Roizman, B. Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes simplex virus-1-infected cell protein 0. Proc. Natl Acad. Sci. USA 99, 7889–7894 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Boutell, C. & Everett, R. D. The herpes simplex virus type 1 (HSV-1) regulatory protein ICP0 interacts with and ubiquitinates p53. J. Biol. Chem. 278, 36596–36602 (2003).

    CAS  PubMed  Google Scholar 

  18. Canning, M., Boutell, C., Parkinson, J. & Everett, R. D. A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7. J. Biol. Chem. 279, 38160–38168 (2004).

    CAS  PubMed  Google Scholar 

  19. Boutell, C., Canning, M., Orr, A. & Everett, R. D. Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase and ubiquitin-specific protease USP7. J. Virol. 79, 12342–12354 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Daubeuf, S. et al. HSV ICP0 recruits USP7 to modulate TLR-mediated innate response. Blood (2008).

  21. Stevenson, P. G., Efstathiou, S., Doherty, P. C. & Lehner, P. J. Inhibition of MHC class I-restricted antigen presentation by γ-2-herpesviruses. Proc. Natl Acad. Sci. USA 97, 8455–8460 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Coscoy, L. & Ganem, D. Kaposi's sarcoma-associated herpesvirus encodes two proteins that block cell surface display of MHC class I chains by enhancing their endocytosis. Proc. Natl Acad. Sci. USA 97, 8051–8056 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Ishido, S., Wang, C., Lee, B. S., Cohen, G. B. & Jung, J. U. Downregulation of major histocompatibility complex class I molecules by Kaposi's sarcoma-associated herpesvirus K3 and K5 proteins. J. Virol. 74, 5300–5309 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Haque, M. et al. Major histocompatibility complex class I molecules are downregulated at the cell surface by the K5 protein encoded by Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8. J. Gen. Virol. 82, 1175–1180 (2001).

    CAS  PubMed  Google Scholar 

  25. Dodd, R. B. et al. Solution structure of the Kaposi's sarcoma-associated herpesvirus K3 N-terminal domain reveals a Novel E2-binding C4HC3-type RING domain. J. Biol. Chem. 279, 53840–53847 (2004).

    CAS  PubMed  Google Scholar 

  26. Ohmura-Hoshino, M. et al. A novel family of membrane-bound E3 ubiquitin ligases. J. Biochem. 140, 147–154 (2006).

    CAS  PubMed  Google Scholar 

  27. Coscoy, L., Sanchez, D. J. & Ganem, D. A novel class of herpesvirus-encoded membrane-bound E3 ubiquitin ligases regulates endocytosis of proteins involved in immune recognition. J. Cell Biol. 155, 1265–1273 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Duncan, L. M. et al. Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules. EMBO J. 25, 1635–1645 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Mansouri, M. et al. The PHD/LAP-domain protein M153R of myxoma virus is a ubiquitin ligase that induces the rapid internalization and lysosomal destruction of CD4. J Virol. 77, 1427–1440 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Lybarger, L., Wang, X., Harris, M. R., Virgin, H. W.t. & Hansen, T. H. Virus subversion of the MHC class I peptide-loading complex. Immunity 18, 121–130 (2003).

    CAS  PubMed  Google Scholar 

  31. Mansouri, M. et al. Kaposi sarcoma herpesvirus K5 removes CD31/PECAM from endothelial cells. Blood 108, 1932–1940 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Hewitt, E. W. et al. Ubiquitylation of MHC class I by the K3 viral protein signals internalization and TSG101-dependent degradation. EMBO J. 21, 2418–2429 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Traub, L. M. & Lukacs, G. L. Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs. J. Cell Sci. 120, 543–553 (2007).

    CAS  PubMed  Google Scholar 

  34. Varadan, R. et al. Solution conformation of Lys 63-linked di-ubiquitin chain provides clues to functional diversity of polyubiquitin signaling. J. Biol. Chem. 279, 7055–7063 (2004).

    CAS  PubMed  Google Scholar 

  35. Barriere, H. et al. Molecular basis of oligoubiquitin-dependent internalization of membrane proteins in mammalian cells. Traffic 7, 282–297 (2006).

    CAS  PubMed  Google Scholar 

  36. Cadwell, K. & Coscoy, L. Ubiquitination on non-lysine residues by a viral E3 ubiquitin ligase. Science 309, 127–130 (2005).

    CAS  PubMed  Google Scholar 

  37. Wang, X. et al. Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3. J. Cell Biol. 177, 613–624 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Boname, J. M., de Lima, B. D., Lehner, P. J. & Stevenson, P. G. Viral degradation of the MHC class I peptide loading complex. Immunity 20, 305–317 (2004).

    CAS  PubMed  Google Scholar 

  39. Nathan, J. A. & Lehner, P. J. The trafficking and regulation of membrane receptors by the RING-CH ubiquitin E3 ligases. Exp. Cell Res. advance online publication, doi:10.1016/j.yexcr.2008.10026 (2008).

  40. Mansouri, M., Rose, P. P., Moses, A. V. & Fruh, K. Remodeling of endothelial adherens junctions by Kaposi's sarcoma-associated herpesvirus. J. Virol. 82, 9615–9628 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Bartee, E. et al. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J. Virol. 78, 1109–1120 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Ohmura-Hoshino, M. et al. Inhibition of MHC class II expression and immune responses by c-MIR. J. Immunol. 177, 341–354 (2006).

    CAS  PubMed  Google Scholar 

  43. Matsuki, Y. et al. Novel regulation of MHC class II function in B cells. EMBO J. 26, 846–854 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. De Gassart, A. et al. MHC class II stabilization at the surface of human dendritic cells is the result of maturation-dependent MARCH I down-regulation. Proc. Natl Acad. Sci. USA 105, 3491–3496 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Bowie, A. G. & Unterholzner, L. Viral evasion and subversion of pattern-recognition receptor signalling. Nature Rev. Immunol. 8, 911–922 (2008).

    CAS  Google Scholar 

  46. Yang, Z., Yan, Z. & Wood, C. Kaposi's sarcoma-associated herpesvirus transactivator RTA promotes degradation of the repressors to regulate viral lytic replication. J. Virol. 82, 3590–3603 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J. & Howley, P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129–1136 (1990).

    CAS  PubMed  Google Scholar 

  48. Beaudenon, S. & Huibregtse, J. M. HPV E6, E6AP and cervical cancer. BMC Biochem. 9 Suppl 1, S4 (2008).

    PubMed  PubMed Central  Google Scholar 

  49. Scheffner, M. & Staub, O. HECT E3s and human disease. BMC Biochem. 8 Suppl 1, S6 (2007).

    PubMed  PubMed Central  Google Scholar 

  50. Camus, S. et al. Ubiquitin-independent degradation of p53 mediated by high-risk human papillomavirus protein E6. Oncogene 26, 4059–4070 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Harada, J. N., Shevchenko, A., Shevchenko, A., Pallas, D. C. & Berk, A. J. Analysis of the adenovirus E1B-55K-anchored proteome reveals its link to ubiquitination machinery. J. Virol. 76, 9194–9206 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Querido, E. et al. Degradation of p53 by adenovirus E4orf6 and E1B55K proteins occurs via a novel mechanism involving a Cullin-containing complex. Genes Dev. 15, 3104–3117 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Blanchette, P. & Branton, P. E. Manipulation of the ubiquitin-proteasome pathway by small DNA tumor viruses. Virology 384, 317–323 (2008).

    PubMed  Google Scholar 

  54. Blanchette, P. et al. Both BC-box motifs of adenovirus protein E4orf6 are required to efficiently assemble an E3 ligase complex that degrades p53. Mol. Cell Biol. 24, 9619–9629 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Malim, M. H. Review. APOBEC proteins and intrinsic resistance to HIV-1 infection. Philos. Trans. R. Soc. Lond B. Biol. Sci. 364, 675–687 (2008).

    PubMed Central  Google Scholar 

  56. Sheehy, A. M., Gaddis, N. C., Choi, J. D. & Malim, M. H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418, 646–650 (2002).

    CAS  PubMed  Google Scholar 

  57. Yu, X. et al. Induction of APOBEC3G ubiquitination and degradation by an HIV-1 Vif-Cul5-SCF complex. Science 302, 1056–1060 (2003).

    CAS  PubMed  Google Scholar 

  58. Mehle, A. et al. Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway. J. Biol. Chem. 279, 7792–7798 (2004).

    CAS  PubMed  Google Scholar 

  59. Liu, B., Sarkis, P. T., Luo, K., Yu, Y. & Yu, X. F. Regulation of Apobec3F and human immunodeficiency virus type 1 Vif by Vif-Cul5-ElonB/C E3 ubiquitin ligase. J. Virol. 79, 9579–9587 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Schrofelbauer, B., Yu, Q., Zeitlin, S. G. & Landau, N. R. Human immunodeficiency virus type 1 Vpr induces the degradation of the UNG and SMUG uracil-DNA glycosylases. J. Virol. 79, 10978–10987 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Randall, R. E. & Goodbourn, S. Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89, 1–47 (2008).

    CAS  PubMed  Google Scholar 

  62. Fontana, J. M., Bankamp, B. & Rota, P. A. Inhibition of interferon induction and signaling by paramyxoviruses. Immunol. Rev. 225, 46–67 (2008).

    CAS  PubMed  Google Scholar 

  63. Li, T., Chen, X., Garbutt, K. C., Zhou, P. & Zheng, N. Structure of DDB1 in complex with a paramyxovirus V protein: viral hijack of a propeller cluster in ubiquitin ligase. Cell 124, 105–117 (2006).

    CAS  PubMed  Google Scholar 

  64. Parisien, J. P., Lau, J. F., Rodriguez, J. J., Ulane, C. M. & Horvath, C. M. Selective STAT protein degradation induced by paramyxoviruses requires both STAT1 and STAT2 but is independent of alpha/beta interferon signal transduction. J. Virol. 76, 4190–4198 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Meusser, B., Hirsch, C., Jarosch, E. & Sommer, T. ERAD: the long road to destruction. Nature Cell Biol. 7, 766–772 (2005).

    CAS  PubMed  Google Scholar 

  66. Nakatsukasa, K. & Brodsky, J. L. The recognition and retrotranslocation of misfolded proteins from the endoplasmic reticulum. Traffic 9, 861–870 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Wiertz, E. J. et al. The human cytomegalovirus US11 gene product dislocates MHC class I heavy chains from the endoplasmic reticulum to the cytosol. Cell 84, 769–779 (1996).

    CAS  PubMed  Google Scholar 

  68. Wiertz, E. J. et al. Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction. Nature 384, 432–438 (1996).

    CAS  PubMed  Google Scholar 

  69. Loureiro, J. & Ploegh, H. L. Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions. Adv. Immunol. 92, 225–305 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Lilley, B. N. & Ploegh, H. L. A membrane protein required for dislocation of misfolded proteins from the ER. Nature 429, 834–840 (2004).

    CAS  PubMed  Google Scholar 

  71. Ye, Y., Shibata, Y., Yun, C., Ron, D. & Rapoport, T. A. A membrane protein complex mediates retro-translocation from the ER lumen into the cytosol. Nature 429, 841–847 (2004).

    CAS  PubMed  Google Scholar 

  72. Mueller, B., Lilley, B. N. & Ploegh, H. L. SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER. J. Cell Biol. 175, 261–270 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Loureiro, J. et al. Signal peptide peptidase is required for dislocation from the endoplasmic reticulum. Nature 441, 894–897 (2006).

    CAS  PubMed  Google Scholar 

  74. Tomazin, R. et al. Cytomegalovirus US2 destroys two components of the MHC class II pathway, preventing recognition by CD4+ T cells. Nature Med. 5, 1039–1043 (1999).

    CAS  PubMed  Google Scholar 

  75. Furman, M. H., Loureiro, J., Ploegh, H. L. & Tortorella, D. Ubiquitinylation of the cytosolic domain of a type I membrane protein is not required to initiate its dislocation from the endoplasmic reticulum. J. Biol. Chem. 278, 34804–34811 (2003).

    CAS  PubMed  Google Scholar 

  76. Hassink, G. C., Barel, M. T., Van Voorden, S. B., Kikkert, M. & Wiertz, E. J. Ubiquitination of MHC class I heavy chains is essential for dislocation by human cytomegalovirus-encoded US2 but not US11. J. Biol. Chem. 281, 30063–30071 (2006).

    CAS  PubMed  Google Scholar 

  77. Schubert, U. et al. CD4 glycoprotein degradation induced by human immunodeficiency virus type 1 Vpu protein requires the function of proteasomes and the ubiquitin-conjugating pathway. J. Virol. 72, 2280–2288 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Margottin, F. et al. A novel human WD protein, h-β TrCp that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol. Cell 1, 565–574 (1998).

    CAS  PubMed  Google Scholar 

  79. Binette, J. et al. Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum. Retrovirology 4, 75 (2007).

    PubMed  PubMed Central  Google Scholar 

  80. Nijman, S. M. et al. A genomic and functional inventory of de-ubiquitinating enzymes. Cell 123, 773–786 (2005).

    CAS  PubMed  Google Scholar 

  81. Sompallae, R. et al. Epstein-Barr virus encodes three bona fide ubiquitin-specific proteases. J. Virol. 82, 10477–10486 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Kattenhorn, L. M., Korbel, G. A., Kessler, B. M., Spooner, E. & Ploegh, H. L. A deubiquitinating enzyme encoded by HSV-1 belongs to a family of cysteine proteases that is conserved across the family Herpesviridae. Mol. Cell 19, 547–557 (2005).

    CAS  PubMed  Google Scholar 

  83. Schlieker, C. et al. Structure of a herpesvirus-encoded cysteine protease reveals a unique class of de-ubiquitinating enzymes. Mol. Cell 25, 677–687 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Bottcher, S. et al. Mutagenesis of the active-site cysteine in the ubiquitin-specific protease contained in large tegument protein pUL36 of pseudorabies virus impairs viral replication in vitro and neuroinvasion in vivo. J. Virol. 82, 6009–6016 (2008).

    PubMed  PubMed Central  Google Scholar 

  85. Jarosinski, K., Kattenhorn, L., Kaufer, B., Ploegh, H. & Osterrieder, N. A herpesvirus ubiquitin-specific protease is critical for efficient T cell lymphoma formation. Proc. Natl Acad. Sci. USA 104, 20025–20030 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Hazes, B. & Read, R. J. Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry 36, 11051–11054 (1997).

    CAS  PubMed  Google Scholar 

  87. Cuconati, A., Mukherjee, C., Perez, D. & White, E. DNA damage response and MCL-1 destruction initiate apoptosis in adenovirus-infected cells. Genes Dev. 17, 2922–2932 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Dimmeler, S., Breitschopf, K., Haendeler, J. & Zeiher, A. M. Dephosphorylation targets Bcl-2 for ubiquitin-dependent degradation: a link between the apoptosome and the proteasome pathway. J. Exp. Med. 189, 1815–1822 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Morita, E. & Sundquist, W. I. Retrovirus budding. Annu. Rev. Cell Dev. Biol. 20, 395–425 (2004).

    CAS  PubMed  Google Scholar 

  90. Martin-Serrano, J. The role of ubiquitin in retroviral egress. Traffic 8, 1297–1303 (2007).

    CAS  PubMed  Google Scholar 

  91. Bieniasz, P. D. Late budding domains and host proteins in enveloped virus release. Virology 344, 55–63 (2006).

    CAS  PubMed  Google Scholar 

  92. Pornillos, O., Alam, S. L., Davis, D. R. & Sundquist, W. I. Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein. Nature Struct. Biol. 9, 812–817 (2002).

    CAS  PubMed  Google Scholar 

  93. Fisher, R. D. et al. Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell 128, 841–852 (2007).

    CAS  PubMed  Google Scholar 

  94. Chung, H. Y. et al. NEDD4L overexpression rescues the release and infectivity of human immunodeficiency virus type 1 constructs lacking PTAP and YPXL late domains. J. Virol. 82, 4884–4897 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Usami, Y., Popov, S., Popova, E. & Gottlinger, H. G. Efficient and specific rescue of human immunodeficiency virus type 1 budding defects by a Nedd4-like ubiquitin ligase. J. Virol. 82, 4898–4907 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Ikeda, F. & Dikic, I. Atypical ubiquitin chains: new molecular signals. 'Protein Modifications: Beyond the Usual Suspects' review series. EMBO Rep. 9, 536–542 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Frias-Staheli, N. et al. Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses. Cell Host Microbe 2, 404–416 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Jin, L., Williamson, A., Banerjee, S., Philipp, I. & Rape, M. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133, 653–665 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Tokunaga, F. et al. Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nature Cell Biol. 11, 123–132 (2009).

    CAS  PubMed  Google Scholar 

  100. Rahighi, S. et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation. Cell 136, 1098–1099 (2009).

    CAS  PubMed  Google Scholar 

  101. Lo, Y. C. et al. Structural basis for recognition of diubiquitins by NEMO. Mol. Cell 33, 602–615 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Petroski, M. D. & Deshaies, R. J. Function and regulation of cullin-RING ubiquitin ligases. Nature Rev. Mol. Cell Biol. 6, 9–20 (2005).

    CAS  Google Scholar 

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Acknowledgements

We thank Jessica Boname, David Komander and members of the Randow and Lehner labs for helpful discussions. We apologize to those authors whose work we have been unable to include because of space constraints. This work was supported by grants from the Wellcome Trust, Medical Research Council and Cambridge University Hospitals Biomedical Research Centre. P.J.L. holds a Lister Institute Research Prize.

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Randow, F., Lehner, P. Viral avoidance and exploitation of the ubiquitin system. Nat Cell Biol 11, 527–534 (2009). https://doi.org/10.1038/ncb0509-527

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