Table of Contents
ISRN Molecular Biology
Volume 2012, Article ID 146748, 9 pages
http://dx.doi.org/10.5402/2012/146748
Review Article

Central Role of Ubiquitination in Genome Maintenance: DNA Replication and Damage Repair

1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA
2Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA

Received 28 October 2011; Accepted 16 November 2011

Academic Editors: C. M. Azzalin, H. A. Heus, and A. Montecucco

Copyright © 2012 Soma Ghosh and Tapas Saha. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. L. DePamphilis and S. D. Bell, Genome Duplication, Garland Publishing, 2010.
  2. D. Branzei and M. Foiani, “Maintaining genome stability at the replication fork,” Nature Reviews Molecular Cell Biology, vol. 11, no. 3, pp. 208–219, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. J. H. J. Hoeijmakers, “Genome maintenance mechanisms for preventing cancer,” Nature, vol. 411, no. 6835, pp. 366–374, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. A. Ciechanover, S. Elias, H. Heller, and A. Hershko, ““Covalent affinity” purification of ubiquitin-activating enzyme,” Journal of Biological Chemistry, vol. 257, no. 5, pp. 2537–2542, 1982. View at Google Scholar · View at Scopus
  5. A. Hershko, H. Heller, S. Elias, and A. Ciechanover, “Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown,” Journal of Biological Chemistry, vol. 258, no. 13, pp. 8206–8214, 1983. View at Google Scholar · View at Scopus
  6. S. M. B. Nijman, M. P. A. Luna-Vargas, A. Velds et al., “A genomic and functional inventory of deubiquitinating enzymes,” Cell, vol. 123, no. 5, pp. 773–786, 2005. View at Publisher · View at Google Scholar · View at Scopus
  7. M. E. Sowa, E. J. Bennett, S. P. Gygi, and J. W. Harper, “Defining the human deubiquitinating enzyme interaction landscape,” Cell, vol. 138, no. 2, pp. 389–403, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. K. Haglund, P. P. Di Fiore, and I. Dikic, “Distinct monoubiquitin signals in receptor endocytosis,” Trends in Biochemical Sciences, vol. 28, no. 11, pp. 598–604, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. A. Shilatifard, “Chromatin modifications by methylation and ubiquitination: implications in the regulation of gene expression,” Annual Review of Biochemistry, vol. 75, pp. 243–269, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. T. T. Huang and A. D. D'Andrea, “Regulation of DNA repair by ubiquitylation,” Nature Reviews Molecular Cell Biology, vol. 7, no. 5, pp. 323–334, 2006. View at Publisher · View at Google Scholar · View at Scopus
  11. M. L. DePamphilis, J. J. Blow, S. Ghosh, T. Saha, K. Noguchi, and A. Vassilev, “Regulating the licensing of DNA replication origins in metazoa,” Current Opinion in Cell Biology, vol. 18, no. 3, pp. 231–239, 2006. View at Publisher · View at Google Scholar · View at Scopus
  12. C. J. Li and M. L. De Pamphilis, “Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division Cycle,” Molecular and Cellular Biology, vol. 22, no. 1, pp. 105–116, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Méndez, X. H. Zou-Yang, S. Y. Kim, M. Hidaka, W. P. Tansey, and B. Stillman, “Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication,” Molecular Cell, vol. 9, no. 3, pp. 481–491, 2002. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Saha, S. Ghosh, A. Vassilev, and M. L. DePamphilis, “Ubiquitylation, phosphorylation and Orc2 modulate the subcellular location of Orc1 and prevent it from inducing apoptosis,” Journal of Cell Science, vol. 119, no. 7, pp. 1371–1382, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. C. M. Pickart, “Mechanisms underlying ubiquitination,” Annual Review of Biochemistry, vol. 70, pp. 503–533, 2001. View at Publisher · View at Google Scholar · View at Scopus
  16. F. Ikeda and I. Dikic, “Atypical ubiquitin chains: new molecular signals. “Protein modifications: beyond the usual Suspects”, review Series,” EMBO Reports, vol. 9, no. 6, pp. 536–542, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. A. J. López-Contreras and O. Fernandez-Capetillo, “The ATR barrier to replication-born DNA damage,” DNA Repair, vol. 9, no. 12, pp. 1249–1255, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. C. Masutani, R. Kusumoto, S. Iwai, and F. Hanaoka, “Mechanisms of accurate translesion synthesis by human DNA polymerase η,” EMBO Journal, vol. 19, no. 12, pp. 3100–3109, 2000. View at Google Scholar · View at Scopus
  19. A. Vaisman, C. Masutani, F. Hanaoka, and S. G. Chaney, “Efficient translesion replication past oxaliplatin and cisplatin GpG adducts by human DNA polymerase η,” Biochemistry, vol. 39, no. 16, pp. 4575–4580, 2000. View at Publisher · View at Google Scholar · View at Scopus
  20. M. F. Goodman and B. Tippin, “Sloppier copier DNA polymerases involved in genome repair,” Current Opinion in Genetics and Development, vol. 10, no. 2, pp. 162–168, 2000. View at Publisher · View at Google Scholar · View at Scopus
  21. T. A. Kunkel and K. Bebenek, “DNA replication fidelity,” Annual Review of Biochemistry, vol. 69, pp. 497–529, 2000. View at Publisher · View at Google Scholar · View at Scopus
  22. C. Lawrence, “The RAD6 DNA repair pathway in Saccharomyces cerevisiae: what does it do, and how does it do it?” BioEssays, vol. 16, no. 4, pp. 253–258, 1994. View at Google Scholar · View at Scopus
  23. T. Saha, J. K. Rih, R. Roy, R. Ballal, and E. M. Rosen, “Transcriptional regulation of the base excision repair pathway by BRCA1,” Journal of Biological Chemistry, vol. 285, no. 25, pp. 19092–19105, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Saha, M. Smulson, and E. M. Rosen, “BRCA1 regulation of base excision repair pathway,” Cell Cycle, vol. 9, no. 13, pp. 2471–2472, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. B. B. S. Zhou and S. J. Elledge, “The DNA damage response: putting checkpoints in perspective,” Nature, vol. 408, no. 6811, pp. 433–439, 2000. View at Publisher · View at Google Scholar · View at Scopus
  26. B. R. Adams, S. E. Golding, R. R. Rao, and K. Valerie, “Dynamic dependence on ATR and ATM for double-Strand break repair in human embryonic stem cells and neural descendants,” PLoS ONE, vol. 5, no. 4, Article ID e10001, 2010. View at Publisher · View at Google Scholar · View at Scopus
  27. S. McNeely, C. Conti, T. Sheikh et al., “Chk1 inhibition after replicative stress activates a double strand break response mediated by ATM and DNA-dependent protein kinase,” Cell Cycle, vol. 9, no. 5, pp. 995–1004, 2010. View at Google Scholar · View at Scopus
  28. F. Ammazzalorso, L. M. Pirzio, M. Bignami, A. Franchitto, and P. Pichierri, “ATR and ATM differently regulate WRN to prevent DSBs at stalled replication forks and promote replication fork recovery,” EMBO Journal, vol. 29, no. 18, pp. 3156–3169, 2010. View at Publisher · View at Google Scholar · View at Scopus
  29. M. B. Kastan and J. Bartek, “Cell-cycle checkpoints and cancer,” Nature, vol. 432, no. 7015, pp. 316–323, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. K. Vermeulen, D. R. Van Bockstaele, and Z. N. Berneman, “The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer,” Cell Proliferation, vol. 36, no. 3, pp. 131–149, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. J. C. Harrison and J. E. Haber, “Surviving the breakup: the DNA damage checkpoint,” Annual Review of Genetics, vol. 40, pp. 209–235, 2006. View at Publisher · View at Google Scholar · View at Scopus
  32. N. Mailand, J. Falck, C. Lukas et al., “Rapid destruction of human Cdc25A in response to DNA damage,” Science, vol. 288, no. 5470, pp. 1425–1429, 2000. View at Publisher · View at Google Scholar · View at Scopus
  33. M. Molinari, C. Mercurio, J. Dominguez, F. Goubin, and G. F. Draetta, “Human Cdc25 A inactivation in response to S phase inhibition and its role in preventing premature mitosis,” EMBO Reports, vol. 1, no. 1, pp. 71–79, 2000. View at Google Scholar · View at Scopus
  34. L. Busino, M. Donzelli, M. Chiesa et al., “Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage,” Nature, vol. 426, no. 6962, pp. 87–91, 2003. View at Publisher · View at Google Scholar · View at Scopus
  35. J. Falck, N. Mailand, R. G. Syljuåsen, J. Bartek, and J. Lukas, “The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis,” Nature, vol. 410, no. 6830, pp. 842–847, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. N. Mailand, S. Bekker-Jensen, J. Bartek, and J. Lukas, “Destruction of claspin by SCFβTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress,” Molecular Cell, vol. 23, no. 3, pp. 307–318, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. I. Mamely, M. A. van Vugt, V. A. Smits et al., “Polo-like kinase-1 controls proteasome-dependent degradation of claspin during checkpoint recovery,” Current Biology, vol. 16, no. 19, pp. 1950–1955, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. A. Peschiaroli, N. V. Dorrello, D. Guardavaccaro et al., “SCFβTrCP-mediated degradation of claspin regulates recovery from the DNA replication checkpoint response,” Molecular Cell, vol. 23, no. 3, pp. 319–329, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. L. N. Bennett and P. R. Clarke, “Regulation of Claspin degradation by the ubiquitin-proteosome pathway during the cell cycle and in response to ATR-dependent checkpoint activation,” FEBS Letters, vol. 580, no. 17, pp. 4176–4181, 2006. View at Publisher · View at Google Scholar · View at Scopus
  40. R. Agami and R. Bernards, “Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle arrest in response to DNA damage,” Cell, vol. 102, no. 1, pp. 55–66, 2000. View at Google Scholar · View at Scopus
  41. F. Bassermann, D. Frescas, D. Guardavaccaro, L. Busino, A. Peschiaroli, and M. Pagano, “The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint,” Cell, vol. 134, no. 2, pp. 256–267, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Ben-Yehoyada, L. C. Wang, I. D. Kozekov, C. J. Rizzo, M. E. Gottesman, and J. Gautier, “Checkpoint signaling from a single DNA interstrand crosslink,” Molecular Cell, vol. 35, no. 5, pp. 704–715, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. I. Garcia-Higuera, T. Taniguchi, S. Ganesan et al., “Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway,” Molecular Cell, vol. 7, no. 2, pp. 249–262, 2001. View at Publisher · View at Google Scholar · View at Scopus
  44. S. Seki, M. Ohzeki, A. Uchida et al., “A requirement of FancL and FancD2 monoubiquitination in DNA repair,” Genes to Cells, vol. 12, no. 3, pp. 299–310, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. S. Hussain, J. B. Wilson, A. L. Medhurst et al., “Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways,” Human Molecular Genetics, vol. 13, no. 12, pp. 1241–1248, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Taniguchi and A. D. D'Andrea, “The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC,” Blood, vol. 100, no. 7, pp. 2457–2462, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. X. Wang, P. R. Andreassen, and A. D. D'Andrea, “Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin,” Molecular and Cellular Biology, vol. 24, no. 13, pp. 5850–5862, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Smogorzewska, S. Matsuoka, P. Vinciguerra et al., “Identification of the FANCI protein, a monoubiquitinated FANCD2 paralog required for DNA Repair,” Cell, vol. 129, no. 2, pp. 289–301, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. J. M. Kim, K. Parmar, M. Huang et al., “Inactivation of murine Usp1 results in genomic instability and a fanconi anemia phenotype,” Developmental Cell, vol. 16, no. 2, pp. 314–320, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. K. Parmar, J. Kim, S. M. Sykes et al., “Hematopoietic stem cell defects in mice with deficiency of Fancd2 or Usp1,” Stem Cells, vol. 28, no. 7, pp. 1188–1195, 2010. View at Publisher · View at Google Scholar · View at Scopus
  51. H. D. Ulrich, “Regulating post-translational modifications of the eukaryotic replication clamp PCNA,” DNA Repair, vol. 8, no. 4, pp. 461–469, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. C. Hoege, B. Pfander, G. L. Moldovan, G. Pyrowolakis, and S. Jentsch, “RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO,” Nature, vol. 419, no. 6903, pp. 135–141, 2002. View at Publisher · View at Google Scholar · View at Scopus
  53. K. Watanabe, S. Tateishi, M. Kawasuji, T. Tsurimoto, H. Inoue, and M. Yamaizumi, “Rad18 guides polη to replication stalling sites through physical interaction and PCNA monoubiquitination,” EMBO Journal, vol. 23, no. 19, pp. 3886–3896, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. P. L. Kannouche, J. Wing, and A. R. Lehmann, “Interaction of human DNA polymerase η with monoubiquitinated PCNA: a possible mechanism for the polymerase switch in response to DNA damage,” Molecular Cell, vol. 14, no. 4, pp. 491–500, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. P. Stelter and H. D. Ulrich, “Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation,” Nature, vol. 425, no. 6954, pp. 188–191, 2003. View at Publisher · View at Google Scholar · View at Scopus
  56. T. Hishida, Y. Kubota, A. M. Carr, and H. Iwasaki, “RAD6-RAD18-RAD5-pathway-dependent tolerance to chronic low-dose ultraviolet light,” Nature, vol. 457, no. 7229, pp. 612–615, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. M. S. Y. Huen, R. Grant, I. Manke et al., “RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly,” Cell, vol. 131, no. 5, pp. 901–914, 2007. View at Publisher · View at Google Scholar · View at Scopus
  58. N. K. Kolas, J. R. Chapman, S. Nakada et al., “Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase,” Science, vol. 318, no. 5856, pp. 1637–1640, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. N. Mailand, S. Bekker-Jensen, H. Faustrup et al., “RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins,” Cell, vol. 131, no. 5, pp. 887–900, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. Y. Xu and B. D. Price, “Chromatin dynamics and the repair of DNA double strand breaks,” Cell Cycle, vol. 10, no. 2, pp. 261–267, 2011. View at Publisher · View at Google Scholar
  61. E. J. Bennett and J. W. Harper, “DNA damage: ubiquitin marks the spot,” Nature Structural and Molecular Biology, vol. 15, no. 1, pp. 20–22, 2008. View at Publisher · View at Google Scholar · View at Scopus
  62. S. Matsuoka, B. A. Ballif, A. Smogorzewska et al., “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage,” Science, vol. 316, no. 5828, pp. 1160–1166, 2007. View at Publisher · View at Google Scholar · View at Scopus
  63. M. Stucki and S. P. Jackson, “γH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes,” DNA Repair, vol. 5, no. 5, pp. 534–543, 2006. View at Publisher · View at Google Scholar · View at Scopus
  64. H. Kim, J. Huang, and J. Chen, “CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA damage response,” Nature Structural and Molecular Biology, vol. 14, no. 8, pp. 710–715, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. Z. Liu, J. Wu, and X. Yu, “CCDC98 targets BRCA1 to DNA damage sites,” Nature Structural and Molecular Biology, vol. 14, no. 8, pp. 716–720, 2007. View at Publisher · View at Google Scholar · View at Scopus
  66. B. Sobhian, G. Shao, D. R. Lilli et al., “RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites,” Science, vol. 316, no. 5828, pp. 1198–1202, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. B. Wang, S. Matsuoka, B. A. Ballif et al., “Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response,” Science, vol. 316, no. 5828, pp. 1194–1198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. S. A. Krum, E. la Rosa Dalugdugan, G. A. Miranda-Carboni, and T. F. Lane, “BRCA1 forms a functional complex with gamma-H2AX as a late response to genotoxic stress,” Journal of Nucleic Acids, p. 801594, 2010. View at Google Scholar
  69. G. Y. Zhao, E. Sonoda, L. J. Barber et al., “A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination,” Molecular Cell, vol. 25, no. 5, pp. 663–675, 2007. View at Publisher · View at Google Scholar · View at Scopus
  70. F. Nicassio, N. Corrado, J. H. A. Vissers et al., “Human USP3 is a chromatin modifier required for S phase progression and genome stability,” Current Biology, vol. 17, no. 22, pp. 1972–1977, 2007. View at Publisher · View at Google Scholar · View at Scopus
  71. M. E. Fitch, S. Nakajima, A. Yasui, and J. M. Ford, “In Vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product,” Journal of Biological Chemistry, vol. 278, no. 47, pp. 46906–46910, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. J. Moser, M. Volker, H. Kool et al., “The UV-damaged DNA binding protein mediates efficient targeting of the nucleotide excision repair complex to UV-induced photo lesions,” DNA Repair, vol. 4, no. 5, pp. 571–582, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. J. E. Cleaver, “Cancer in xeroderma pigmentosum and related disorders of DNA repair,” Nature Reviews Cancer, vol. 5, no. 7, pp. 564–573, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. A. Al-Hakim, C. Escribano-Diaz, M. C. Landry et al., “The ubiquitous role of ubiquitin in the DNA damage response,” DNA Repair, vol. 9, no. 12, pp. 1229–1240, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. D. Komander, F. Reyes-Turcu, J. D. F. Licchesi, P. Odenwaelder, K. D. Wilkinson, and D. Barford, “Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains,” EMBO Reports, vol. 10, no. 5, pp. 466–473, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. F. E. Reyes-Turcu and K. D. Wilkinson, “Polyubiquitin binding and disassembly by deubiquitinating enzymes,” Chemical Reviews, vol. 109, no. 4, pp. 1495–1508, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. V. H. Oestergaard, F. Langevin, H. J. Kuiken et al., “Deubiquitination of FANCD2 is required for DNA crosslink repair,” Molecular Cell, vol. 28, no. 5, pp. 798–809, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Guterman and M. H. Glickman, “Deubiquitinating enzymes are IN(trinsic to proteasome function),” Current Protein and Peptide Science, vol. 5, no. 3, pp. 201–211, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. J. Hanna, D. S. Leggett, and D. Finley, “Ubiquitin depletion as a key mediator of toxicity by translational inhibitors,” Molecular and Cellular Biology, vol. 23, no. 24, pp. 9251–9261, 2003. View at Publisher · View at Google Scholar · View at Scopus
  80. W. H. Park, S. Margossian, A. A. Horwitz, A. M. Simons, A. D. D'Andrea, and J. D. Parvin, “Direct DNA binding activity of the Fanconi anemia D2 protein,” Journal of Biological Chemistry, vol. 280, no. 25, pp. 23593–23598, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. E. G. Mimnaugh, M. K. Yunmbam, Q. Li et al., “Prevention of cisplatin-DNA adduct repair and potentiation of cisplatin-induced apoptosis in ovarian carcinoma cells by proteasome inhibitors,” Biochemical Pharmacology, vol. 60, no. 9, pp. 1343–1354, 2000. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Dornan, I. Wertz, H. Shimizu et al., “The ubiquitin ligase COP1 is a critical negative regulator of p53,” Nature, vol. 429, no. 6987, pp. 86–92, 2004. View at Publisher · View at Google Scholar · View at Scopus
  83. Y. H. Lee, J. B. Andersen, H. T. Song et al., “Definition of ubiquitination modulator COP1 as a novel therapeutic target in human hepatocellular carcinoma,” Cancer Research, vol. 70, no. 21, pp. 8264–8269, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. D. M. Duda, D. C. Scott, M. F. Calabrese, E. S. Zimmerman, N. Zheng, and B. A. Schulman, “Structural regulation of cullin-RING ubiquitin ligase complexes,” Current Opinion in Structural Biology, vol. 21, no. 2, pp. 257–264, 2011. View at Publisher · View at Google Scholar
  85. T. A. Soucy, P. G. Smith, M. A. Milhollen et al., “An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer,” Nature, vol. 458, no. 7239, pp. 732–736, 2009. View at Publisher · View at Google Scholar · View at Scopus
  86. T. A. Soucy, P. G. Smith, and M. Rolfe, “Targeting NEDD8-activated cullin-RING ligases for the treatment of cancer,” Clinical Cancer Research, vol. 15, no. 12, pp. 3912–3916, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. Y. Liu, H. A. Lashuel, S. Choi et al., “Discovery of inhibitors that elucidate the role of UCH-L1 activity in the H1299 lung cancer cell line,” Chemistry and Biology, vol. 10, no. 9, pp. 837–846, 2003. View at Publisher · View at Google Scholar · View at Scopus
  88. A. H. Mermerian, A. Case, R. L. Stein, and G. D. Cuny, “Structure-activity relationship, kinetic mechanism, and selectivity for a new class of ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitors,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 13, pp. 3729–3732, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. K. Ratia, S. Pegan, J. Takayama et al., “A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replication,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 42, pp. 16119–16124, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. J. J. Driscoll and R. DeChowdhury, “Therapeutically targeting the SUMOylation, Ubiquitination and Proteasome pathways as a novel anticancer strategy,” Targeted Oncology, vol. 5, pp. 281–289, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. F. Colland, “The therapeutic potential of deubiquitinating enzyme inhibitors,” Biochemical Society Transactions, vol. 38, no. 1, pp. 137–143, 2010. View at Publisher · View at Google Scholar · View at Scopus