Breaking the chains: structure and function of the deubiquitinases
10.1038/nrm2731
Crossref journal-article
Springer Science and Business Media LLC
Nature Reviews Molecular Cell Biology (297)
Bibliography

Komander, D., Clague, M. J., & Urbé, S. (2009). Breaking the chains: structure and function of the deubiquitinases. Nature Reviews Molecular Cell Biology, 10(8), 550–563.

Authors 3
  1. David Komander (first)
  2. Michael J. Clague (additional)
  3. Sylvie Urbé (additional)
References 138 Referenced 1,775
  1. Peng, J. et al. A proteomics approach to understanding protein ubiquitination. Nature Biotech. 21, 921–926 (2003). (10.1038/nbt849) / Nature Biotech. by J Peng (2003)
  2. Meierhofer, D., Wang, X., Huang, L. & Kaiser, P. Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J. Proteome Res. 10, 4566–4576 (2008). (10.1021/pr800468j) / J. Proteome Res. by D Meierhofer (2008)
  3. Ikeda, F. & Dikic, I. Atypical ubiquitin chains: new molecular signals. 'Protein modifications: beyond the usual suspects' review series. EMBO Rep. 9, 536–542 (2008). (10.1038/embor.2008.93) / EMBO Rep. by F Ikeda (2008)
  4. Scheel, H. Comparative Analysis of the Ubiquitin-Proteasome System in Homo sapiens and Saccharomyces cerevisiae. Thesis, Univ. Cologne (2005). Highly comprehensive bioinformatic study of the ubiquitin–proteasome system, which deserves a wide readership.
  5. Nijman, S. M. et al. A genomic and functional inventory of deubiquitinating enzymes. Cell 123, 773–786 (2005). (10.1016/j.cell.2005.11.007) / Cell by SM Nijman (2005)
  6. Hurley, J. H., Lee, S. & Prag, G. Ubiquitin-binding domains. Biochem. J. 399, 361–372 (2006). (10.1042/BJ20061138) / Biochem. J. by JH Hurley (2006)
  7. Zhu, X., Menard, R. & Sulea, T. High incidence of ubiquitin-like domains in human ubiquitin-specific proteases. Proteins 69, 1–7 (2007). (10.1002/prot.21546) / Proteins by X Zhu (2007)
  8. Edelmann, M. J. & Kessler, B. M. Ubiquitin and ubiquitin-like specific proteases targeted by infectious pathogens: emerging patterns and molecular principles. Biochim. Biophys. Acta 1782, 809–816 (2008). (10.1016/j.bbadis.2008.08.010) / Biochim. Biophys. Acta by MJ Edelmann (2008)
  9. Komander, D. & Barford, D. Structure of the A20 OTU domain and mechanistic insights into deubiquitination. Biochem. J. 409, 77–85 (2008). (10.1042/BJ20071399) / Biochem. J. by D Komander (2008)
  10. Storer, A. C. & Menard, R. Catalytic mechanism in papain family of cysteine peptidases. Methods Enzymol. 244, 486–500 (1994). (10.1016/0076-6879(94)44035-2) / Methods Enzymol. by AC Storer (1994)
  11. Hu, M. et al. Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde. Cell 111, 1041–1054 (2002). The first USP domain structure, in the presence and absence of ubiquitin. It defined the USP fold and revealed conformational changes on ubiquitin binding. (10.1016/S0092-8674(02)01199-6) / Cell by M Hu (2002)
  12. Reyes-Turcu, F. E., Shanks, J. R., Komander, D. & Wilkinson, K. D. Recognition of polyubiquitin isoforms by the multiple ubiquitin binding modules of isopeptidase T. J. Biol. Chem. 283, 19581–19592 (2008). (10.1074/jbc.M800947200) / J. Biol. Chem. by FE Reyes-Turcu (2008)
  13. Hu, M. et al. Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 24, 3747–3756 (2005). (10.1038/sj.emboj.7600832) / EMBO J. by M Hu (2005)
  14. Avvakumov, G. V. et al. Amino-terminal dimerization, NRDP1–rhodanese interaction, and inhibited catalytic domain conformation of the ubiquitin-specific protease 8 (USP8). J. Biol. Chem. 281, 38061–38070 (2006). (10.1074/jbc.M606704200) / J. Biol. Chem. by GV Avvakumov (2006)
  15. Komander, D. et al. The structure of the CYLD USP domain explains its specificity for Lys63-linked polyubiquitin and reveals a B box module. Mol. Cell 29, 451–464 (2008). Provides a rationale for the Lys63-linked ubiquitin chain specificity of CYLD. (10.1016/j.molcel.2007.12.018) / Mol. Cell by D Komander (2008)
  16. Edelmann, M. J. et al. Structural basis and specificity of human otubain 1-mediated deubiquitination. Biochem. J. 418, 379–390 (2009). (10.1042/BJ20081318) / Biochem. J. by MJ Edelmann (2009)
  17. Lin, S. C. et al. Molecular basis for the unique deubiquitinating activity of the NF-κB inhibitor A20. J. Mol. Biol. 376, 526–540 (2008). (10.1016/j.jmb.2007.11.092) / J. Mol. Biol. by SC Lin (2008)
  18. Nanao, M. H. et al. Crystal structure of human otubain 2. EMBO Rep. 5, 783–788 (2004). (10.1038/sj.embor.7400201) / EMBO Rep. by MH Nanao (2004)
  19. Messick, T. E. et al. Structural basis for ubiquitin recognition by the Otu1 ovarian tumor domain protein. J. Biol. Chem. 283, 11038–11049 (2008). (10.1074/jbc.M704398200) / J. Biol. Chem. by TE Messick (2008)
  20. Johnston, S. C., Larsen, C. N., Cook, W. J., Wilkinson, K. D. & Hill, C. P. Crystal structure of a deubiquitinating enzyme (human UCH-L3) at 1.8 A resolution. EMBO J. 16, 3787–3796 (1997). (10.1093/emboj/16.13.3787) / EMBO J. by SC Johnston (1997)
  21. Johnston, S. C., Riddle, S. M., Cohen, R. E. & Hill, C. P. Structural basis for the specificity of ubiquitin C-terminal hydrolases. EMBO J. 18, 3877–3887 (1999). (10.1093/emboj/18.14.3877) / EMBO J. by SC Johnston (1999)
  22. Komander, D. et al. Molecular discrimination of structurally equivalent Lys63-linked and linear polyubiquitin chains. EMBO Rep. 5, 466–473 (2009). First survey of ubiquitin chain linkage specificities across DUB families. (10.1038/embor.2009.55) / EMBO Rep. by D Komander (2009)
  23. Popp, M. W., Artavanis-Tsakonas, K. & Ploegh, H. L. Substrate filtering by the active site crossover loop in UCHL3 revealed by sortagging and gain-of-function mutations. J. Biol. Chem. 284, 3593–3602 (2009). The active site crossover loop in UCHL3 requires extension to allow polyubiquitin chain cleavage. (10.1074/jbc.M807172200) / J. Biol. Chem. by MW Popp (2009)
  24. Larsen, C. N., Krantz, B. A. & Wilkinson, K. D. Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry 37, 3358–3368 (1998). (10.1021/bi972274d) / Biochemistry by CN Larsen (1998)
  25. Riess, O., Rub, U., Pastore, A., Bauer, P. & Schols, L. SCA3: neurological features, pathogenesis and animal models. Cerebellum 7, 125–137 (2008). (10.1007/s12311-008-0013-4) / Cerebellum by O Riess (2008)
  26. Nicastro, G. et al. The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition. Proc. Natl Acad. Sci. USA 102, 10493–10498 (2005). Together with references 27 and 28, this paper reveals the large conformational changes exhibited by the Josephinfamily of DUBs. (10.1073/pnas.0501732102) / Proc. Natl Acad. Sci. USA by G Nicastro (2005)
  27. Mao, Y. et al. Deubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain. Proc. Natl Acad. Sci. USA 102, 12700–12705 (2005). (10.1073/pnas.0506344102) / Proc. Natl Acad. Sci. USA by Y Mao (2005)
  28. Nicastro, G. et al. The josephin domain of ataxin-3 contains two distinct ubiquitin binding motifs. Biopolymers 20 Apr 2009 (doi:10.1002/bip.21210).
  29. Sato, Y. et al. Structural basis for specific cleavage of Lys 63-linked polyubiquitin chains. Nature 455, 358–362 (2008). The first structure of a DUB with a diubiquitin bound across the active site. It revealed the mechanism of action of JAMM/MPN+ proteases and suggested a rationale for the Lys63-linked ubiquitin chain specificity of AMSH-LP. (10.1038/nature07254) / Nature by Y Sato (2008)
  30. Tran, H. J., Allen, M. D., Lowe, J. & Bycroft, M. Structure of the Jab1/MPN domain and its implications for proteasome function. Biochemistry 42, 11460–11465 (2003). (10.1021/bi035033g) / Biochemistry by HJ Tran (2003)
  31. Maytal-Kivity, V., Reis, N., Hofmann, K. & Glickman, M. H. MPN+, a putative catalytic motif found in a subset of MPN domain proteins from eukaryotes and prokaryotes, is critical for Rpn11 function. BMC Biochem. 3, 28 (2002). (10.1186/1471-2091-3-28) / BMC Biochem. by V Maytal-Kivity (2002)
  32. Yao, T. & Cohen, R. E. A cryptic protease couples deubiquitination and degradation by the proteasome. Nature 419, 403–407 (2002). (10.1038/nature01071) / Nature by T Yao (2002)
  33. Cope, G. A. et al. Role of predicted metalloprotease motif of Jab1/Csn5 in cleavage of Nedd8 from Cul1. Science 298, 608–611 (2002). (10.1126/science.1075901) / Science by GA Cope (2002)
  34. McCullough, J. et al. Activation of the endosome-associated ubiquitin isopeptidase AMSH by STAM, a component of the multivesicular body-sorting machinery. Curr. Biol. 16, 160–165 (2006). (10.1016/j.cub.2005.11.073) / Curr. Biol. by J McCullough (2006)
  35. Dong, Y. et al. Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. Mol. Cell 12, 1087–1099 (2003). (10.1016/S1097-2765(03)00424-6) / Mol. Cell by Y Dong (2003)
  36. Wang, B. & Elledge, S. J. Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. Proc. Natl Acad. Sci. USA 104, 20759–20763 (2007). (10.1073/pnas.0710061104) / Proc. Natl Acad. Sci. USA by B Wang (2007)
  37. Shao, G. et al. The Rap80–BRCC36 de-ubiquitinating enzyme complex antagonizes RNF8–Ubc13-dependent ubiquitination events at DNA double strand breaks. Proc. Natl Acad. Sci. USA 106, 3166–3171 (2009). (10.1073/pnas.0807485106) / Proc. Natl Acad. Sci. USA by G Shao (2009)
  38. Cooper, E. M. et al. K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1. EMBO J. 28, 621–631 (2009). (10.1038/emboj.2009.27) / EMBO J. by EM Cooper (2009)
  39. Drag, M. et al. Positional-scanning fluorigenic substrate libraries reveal unexpected specificity determinants of DUBs (deubiquitinating enzymes). Biochem. J. 415, 367–375 (2008). (10.1042/BJ20080779) / Biochem. J. by M Drag (2008)
  40. Catic, A. et al. Screen for ISG15-crossreactive deubiquitinases. PLoS ONE 2, e679 (2007). (10.1371/journal.pone.0000679) / PLoS ONE by A Catic (2007)
  41. 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). (10.1016/j.chom.2007.09.014) / Cell Host Microbe by N Frias-Staheli (2007)
  42. Malakhov, M. P., Malakhova, O. A., Kim, K. I., Ritchie, K. J. & Zhang, D. E. UBP43 (USP18) specifically removes ISG15 from conjugated proteins. J. Biol. Chem. 277, 9976–9981 (2002). (10.1074/jbc.M109078200) / J. Biol. Chem. by MP Malakhov (2002)
  43. Gong, L., Kamitani, T., Millas, S. & Yeh, E. T. Identification of a novel isopeptidase with dual specificity for ubiquitin- and NEDD8-conjugated proteins. J. Biol. Chem. 275, 14212–14216 (2000). (10.1074/jbc.275.19.14212) / J. Biol. Chem. by L Gong (2000)
  44. Tokunaga, F. et al. Involvement of linear polyubiquitylation of NEMO in NF-κB activation. Nature Cell Biol. 11, 123–132 (2009). (10.1038/ncb1821) / Nature Cell Biol. by F Tokunaga (2009)
  45. Rahighi, S. et al. Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation. Cell 136, 1098–1109 (2009). (10.1016/j.cell.2009.03.007) / Cell by S Rahighi (2009)
  46. Huang, T. T. et al. Regulation of monoubiquitinated PCNA by DUB autocleavage. Nature Cell Biol. 8, 339–347 (2006). / Nature Cell Biol. by TT Huang (2006)
  47. Wang, T. et al. Evidence for bidentate substrate binding as the basis for the K48 linkage specificity of otubain 1. J. Mol. Biol. 386, 1011–1023 (2009). (10.1016/j.jmb.2008.12.085) / J. Mol. Biol. by T Wang (2009)
  48. Tran, H., Hamada, F., Schwarz-Romond, T. & Bienz, M. Trabid, a new positive regulator of Wnt-induced transcription with preference for binding and cleaving K63-linked ubiquitin chains. Genes Dev. 22, 528–542 (2008). (10.1101/gad.463208) / Genes Dev. by H Tran (2008)
  49. Kayagaki, N. et al. DUBA: a deubiquitinase that regulates type I interferon production. Science 318, 1628–1632 (2007). (10.1126/science.1145918) / Science by N Kayagaki (2007)
  50. McCullough, J., Clague, M. J. & Urbe, S. AMSH is an endosome-associated ubiquitin isopeptidase. J. Cell Biol. 166, 487–492 (2004). First direct demonstration of in vitro chain linkage specificity and proposed function in regulating receptor fate. (10.1083/jcb.200401141) / J. Cell Biol. by J McCullough (2004)
  51. Nakamura, M., Tanaka, N., Kitamura, N. & Komada, M. Clathrin anchors deubiquitinating enzymes, AMSH and AMSH-like protein, on early endosomes. Genes Cells 11, 593–606 (2006). (10.1111/j.1365-2443.2006.00963.x) / Genes Cells by M Nakamura (2006)
  52. Winborn, B. J. et al. The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains. J. Biol. Chem. 283, 26436–26443 (2008). (10.1074/jbc.M803692200) / J. Biol. Chem. by BJ Winborn (2008)
  53. Al-Hakim, A. K. et al. Control of AMPK-related kinases by USP9X and atypical Lys29/Lys33-linked polyubiquitin chains. Biochem. J. 411, 249–260 (2008). (10.1042/BJ20080067) / Biochem. J. by AK Al-Hakim (2008)
  54. Reyes-Turcu, F. E. et al. The ubiquitin binding domain ZnF UBP recognizes the C-terminal diglycine motif of unanchored ubiquitin. Cell 124, 1197–1208 (2006). Defines a new mode of ubiquitin recognition and allosteric regulation of DUB activity. (10.1016/j.cell.2006.02.038) / Cell by FE Reyes-Turcu (2006)
  55. Amerik, A., Swaminathan, S., Krantz, B. A., Wilkinson, K. D. & Hochstrasser, M. In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome. EMBO J. 16, 4826–4838 (1997). (10.1093/emboj/16.16.4826) / EMBO J. by A Amerik (1997)
  56. Hunter, T. The age of crosstalk: phosphorylation, ubiquitination, and beyond. Mol. Cell 28, 730–738 (2007). (10.1016/j.molcel.2007.11.019) / Mol. Cell by T Hunter (2007)
  57. Reiley, W., Zhang, M., Wu, X., Granger, E. & Sun, S. C. Regulation of the deubiquitinating enzyme CYLD by IκB kinase gamma-dependent phosphorylation. Mol. Cell. Biol. 25, 3886–3895 (2005). (10.1128/MCB.25.10.3886-3895.2005) / Mol. Cell. Biol. by W Reiley (2005)
  58. Mizuno, E., Kitamura, N. & Komada, M. 14-3-3-dependent inhibition of the deubiquitinating activity of UBPY and its cancellation in the M phase. Exp. Cell Res. 313, 3624–3634 (2007). (10.1016/j.yexcr.2007.07.028) / Exp. Cell Res. by E Mizuno (2007)
  59. Pohl, C. & Jentsch, S. Final stages of cytokinesis and midbody ring formation are controlled by BRUCE. Cell 132, 832–845 (2008). (10.1016/j.cell.2008.01.012) / Cell by C Pohl (2008)
  60. Mukai, A. et al. Dynamic regulation of ubiquitylation and deubiquitylation at the central spindle during cytokinesis. J. Cell Sci. 121, 1325–1333 (2008). (10.1242/jcs.027417) / J. Cell Sci. by A Mukai (2008)
  61. Todi, S. V. et al. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J. 28, 372–382 (2009). (10.1038/emboj.2008.289) / EMBO J. by SV Todi (2009)
  62. Meulmeester, E., Kunze, M., Hsiao, H. H., Urlaub, H. & Melchior, F. Mechanism and consequences for paralog-specific sumoylation of ubiquitin-specific protease 25. Mol. Cell 30, 610–619 (2008). (10.1016/j.molcel.2008.03.021) / Mol. Cell by E Meulmeester (2008)
  63. Ross, S. H. et al. Differential redox regulation within the PTP superfamily. Cell Signal. 19, 1521–1530 (2007). (10.1016/j.cellsig.2007.01.026) / Cell Signal. by SH Ross (2007)
  64. Enesa, K. et al. Hydrogen peroxide prolongs nuclear localization of NF-κB in activated cells by suppressing negative regulatory mechanisms. J. Biol. Chem. 283, 18582–18590 (2008). Suggests that DUBs of the NF-κB pathway might be targets of reactive oxygen species. (10.1074/jbc.M801312200) / J. Biol. Chem. by K Enesa (2008)
  65. 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). (10.1038/ni1561) / Nature Immunol. by B Coornaert (2008)
  66. Row, P. E. et al. The MIT domain of UBPY constitutes a CHMP binding and endosomal localization signal required for efficient epidermal growth factor receptor degradation. J. Biol. Chem. 282, 30929–30937 (2007). (10.1074/jbc.M704009200) / J. Biol. Chem. by PE Row (2007)
  67. Iha, H. et al. Inflammatory cardiac valvulitis in TAX1BP1-deficient mice through selective NF-κB activation. EMBO J. 27, 629–641 (2008). (10.1038/emboj.2008.5) / EMBO J. by H Iha (2008)
  68. Wagner, S. et al. Ubiquitin binding mediates the NF-κB inhibitory potential of ABIN proteins. Oncogene 27, 3739–3745 (2008). (10.1038/sj.onc.1211042) / Oncogene by S Wagner (2008)
  69. Yao, T. et al. Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex. Mol. Cell 31, 909–917 (2008). (10.1016/j.molcel.2008.08.027) / Mol. Cell by T Yao (2008)
  70. Kimura, Y. et al. An inhibitor of a deubiquitinating enzyme regulates ubiquitin homeostasis. Cell 137, 549–559 (2009). (10.1016/j.cell.2009.02.028) / Cell by Y Kimura (2009)
  71. Ventii, K. H. & Wilkinson, K. D. Protein partners of deubiquitinating enzymes. Biochem. J. 414, 161–175 (2008). (10.1042/BJ20080798) / Biochem. J. by KH Ventii (2008)
  72. Cohn, M. A. et al. A UAF1-containing multisubunit protein complex regulates the Fanconi anemia pathway. Mol. Cell 28, 786–797 (2007). Together with reference 73, this paper shows that a WD40 protein can allosterically activate three DUBs of the USP family. (10.1016/j.molcel.2007.09.031) / Mol. Cell by MA Cohn (2007)
  73. Cohn, M. A., Kee, Y., Haas, W., Gygi, S. P. & D'Andrea, A. D. UAF1 is a subunit of multiple deubiquitinating enzyme complexes. J. Biol. Chem. 8, 5343–5351 (2008). / J. Biol. Chem. by MA Cohn (2008)
  74. Sowa, M. E., Bennett, E. J., Gygi, S. P. & Harper, J. W. Defining the human deubiquitinating enzyme interaction landscape. Cell 16 Jul 2009 (doi: 10.1016/j.cell.2009.04.042). Comprehensive proteomic study of the interaction profiles of 75 human DUBs. (10.1016/j.cell.2009.04.042)
  75. van der Knaap, J. A. et al. GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7. Mol. Cell 17, 695–707 (2005). (10.1016/j.molcel.2005.02.013) / Mol. Cell by JA van der Knaap (2005)
  76. Row, P. E., Prior, I. A., McCullough, J., Clague, M. J. & Urbe, S. The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation. J. Biol. Chem. 281, 12618–12624 (2006). (10.1074/jbc.M512615200) / J. Biol. Chem. by PE Row (2006)
  77. Blagoev, B., Ong, S. E., Kratchmarova, I. & Mann, M. Temporal analysis of phosphotyrosine-dependent signaling networks by quantitative proteomics. Nature Biotech. 22, 1139–1145 (2004). (10.1038/nbt1005) / Nature Biotech. by B Blagoev (2004)
  78. Nakamura, N. & Hirose, S. Regulation of mitochondrial morphology by USP30, a deubiquitinating enzyme present in the mitochondrial outer membrane. Mol. Biol. Cell 19, 1903–1911 (2008). (10.1091/mbc.e07-11-1103) / Mol. Biol. Cell by N Nakamura (2008)
  79. Endo, A. et al. Nucleolar structure and function are regulated by the deubiquitylating enzyme USP36. J. Cell Sci. 122, 678–686 (2009). (10.1242/jcs.044461) / J. Cell Sci. by A Endo (2009)
  80. Lauwers, E., Jacob, C. & Andre, B. K63-linked ubiquitin chains as a specific signal for protein sorting into the multivesicular body pathway. J. Cell Biol. 3, 493–502 (2009). (10.1083/jcb.200810114) / J. Cell Biol. by E Lauwers (2009)
  81. Xu, P. et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137, 133–145 (2009). (10.1016/j.cell.2009.01.041) / Cell by P Xu (2009)
  82. Daviet, L. & Colland, F. Targeting ubiquitin specific proteases for drug discovery. Biochimie 90, 270–283 (2008). (10.1016/j.biochi.2007.09.013) / Biochimie by L Daviet (2008)
  83. Nicholson, B., Marblestone, J. G., Butt, T. R. & Mattern, M. R. Deubiquitinating enzymes as novel anticancer targets. Future Oncol. 3, 191–199 (2007). (10.2217/14796694.3.2.191) / Future Oncol. by B Nicholson (2007)
  84. Hoeller, D. & Dikic, I. Targeting the ubiquitin system in cancer therapy. Nature 458, 438–444 (2009). (10.1038/nature07960) / Nature by D Hoeller (2009)
  85. Graner, E. et al. The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell 5, 253–261 (2004). This paper, together with references 86 and 87, highlights the potential relevance of DUBs as therapeutic drug targets. (10.1016/S1535-6108(04)00055-8) / Cancer Cell by E Graner (2004)
  86. Popov, N. et al. The ubiquitin-specific protease USP28 is required for MYC stability. Nature Cell Biol. 9, 765–774 (2007). (10.1038/ncb1601) / Nature Cell Biol. by N Popov (2007)
  87. Cummins, J. M. & Vogelstein, B. HAUSP is required for p53 destabilization. Cell Cycle 3, 689–692 (2004). (10.4161/cc.3.6.924) / Cell Cycle by JM Cummins (2004)
  88. Stegmeier, F. et al. Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature 446, 876–881 (2007). Highlights the crucial role for USP44 in the progression of the cell cycle. (10.1038/nature05694) / Nature by F Stegmeier (2007)
  89. Huang, F., Kirkpatrick, D., Jiang, X., Gygi, S. & Sorkin, A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol. Cell 21, 737–748 (2006). (10.1016/j.molcel.2006.02.018) / Mol. Cell by F Huang (2006)
  90. Clague, M. J. & Urbe, S. Endocytosis: the DUB version. Trends Cell Biol. 16, 551–559 (2006). (10.1016/j.tcb.2006.09.002) / Trends Cell Biol. by MJ Clague (2006)
  91. Butterworth, M. B. et al. The deubiquitinating enzyme UCH-L3 regulates the apical membrane recycling of the epithelial sodium channel. J. Biol. Chem. 282, 37885–37893 (2007). (10.1074/jbc.M707989200) / J. Biol. Chem. by MB Butterworth (2007)
  92. Mizuno, E., Kobayashi, K., Yamamoto, A., Kitamura, N. & Komada, M. A deubiquitinating enzyme UBPY regulates the level of protein ubiquitination on endosomes. Traffic 7, 1017–1031 (2006). (10.1111/j.1600-0854.2006.00452.x) / Traffic by E Mizuno (2006)
  93. Boulkroun, S. et al. Vasopressin-inducible ubiquitin-specific protease 10 increases ENaC cell surface expression by deubiquitylating and stabilizing sorting nexin 3. Am. J. Physiol. Renal Physiol. 295, F889–F900 (2008). (10.1152/ajprenal.00001.2008) / Am. J. Physiol. Renal Physiol. by S Boulkroun (2008)
  94. Li, Z. et al. Ubiquitination of a novel deubiquitinating enzyme requires direct binding to von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 277, 4656–4662 (2002). (10.1074/jbc.M108269200) / J. Biol. Chem. by Z Li (2002)
  95. Lu, Y. et al. USP19 deubiquitinating enzyme supports cell proliferation by stabilizing KPC1, a ubiquitin ligase for p27Kip1. Mol. Cell Biol. 29, 547–558 (2009). (10.1128/MCB.00329-08) / Mol. Cell Biol. by Y Lu (2009)
  96. Cao, Z., Wu, X., Yen, L., Sweeney, C. & Carraway, K. L. Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1. Mol. Cell. Biol. 27, 2180–2188 (2007). (10.1128/MCB.01245-06) / Mol. Cell. Biol. by Z Cao (2007)
  97. Brummelkamp, T. R., Nijman, S. M., Dirac, A. M. & Bernards, R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-κB. Nature 424, 797–801 (2003). Together with references 98 and 99, this study put the spotlight on the tumour suppressor function of a DUB. (10.1038/nature01811) / Nature by TR Brummelkamp (2003)
  98. Trompouki, E. et al. CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members. Nature 424, 793–796 (2003). (10.1038/nature01803) / Nature by E Trompouki (2003)
  99. Kovalenko, A. et al. The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination. Nature 424, 801–805 (2003). (10.1038/nature01802) / Nature by A Kovalenko (2003)
  100. Brooks, C. L., Li, M., Hu, M., Shi, Y. & Gu, W. The p53–Mdm2–HAUSP complex is involved in p53 stabilization by HAUSP. Oncogene 26, 7262–7266 (2007). (10.1038/sj.onc.1210531) / Oncogene by CL Brooks (2007)
  101. Heyninck, K. & Beyaert, R. A20 inhibits NF-κB activation by dual ubiquitin-editing functions. Trends Biochem. Sci. 30, 1–4 (2005). (10.1016/j.tibs.2004.11.001) / Trends Biochem. Sci. by K Heyninck (2005)
  102. Verma, R. et al. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 298, 611–615 (2002). (10.1126/science.1075898) / Science by R Verma (2002)
  103. Koulich, E., Li, X. & Demartino, G. N. Relative structural and functional roles of multiple deubiquitylating proteins associated with mammalian 26S proteasome. Mol. Biol. Cell 19, 1072–1082 (2008). (10.1091/mbc.e07-10-1040) / Mol. Biol. Cell by E Koulich (2008)
  104. Crosas, B. et al. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell 127, 1401–1413 (2006). (10.1016/j.cell.2006.09.051) / Cell by B Crosas (2006)
  105. Leggett, D. S. et al. Multiple associated proteins regulate proteasome structure and function. Mol. Cell 10, 495–507 (2002). (10.1016/S1097-2765(02)00638-X) / Mol. Cell by DS Leggett (2002)
  106. Yao, T. et al. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nature Cell Biol. 8, 994–1002 (2006). (10.1038/ncb1460) / Nature Cell Biol. by T Yao (2006)
  107. Hanna, J., Meides, A., Zhang, D. P. & Finley, D. A ubiquitin stress response induces altered proteasome composition. Cell 129, 747–759 (2007). (10.1016/j.cell.2007.03.042) / Cell by J Hanna (2007)
  108. Hanna, J. et al. Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 127, 99–111 (2006). (10.1016/j.cell.2006.07.038) / Cell by J Hanna (2006)
  109. Amerik, A. Y., Nowak, J., Swaminathan, S. & Hochstrasser, M. The DoA4 deubiquitinating enzyme is functionally linked to the vacuolar protein-sorting and endocytic pathways. Mol. Biol. Cell 11, 3365–3380 (2000). (10.1091/mbc.11.10.3365) / Mol. Biol. Cell by AY Amerik (2000)
  110. Dayal, S. et al. Suppression of the deubiquitinating enzyme USP5 causes the accumulation of unanchored polyubiquitin and the activation of p53. J. Biol. Chem. 8, 5030–5041 (2008). / J. Biol. Chem. by S Dayal (2008)
  111. Amerik, A. Y., Li, S. J. & Hochstrasser, M. Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiae. Biol. Chem. 381, 981–992 (2000). (10.1515/BC.2000.121) / Biol. Chem. by AY Amerik (2000)
  112. Kirkin, V. & Dikic, I. Role of ubiquitin- and Ubl-binding proteins in cell signaling. Curr. Opin. Cell Biol. 19, 199–205 (2007). (10.1016/j.ceb.2007.02.002) / Curr. Opin. Cell Biol. by V Kirkin (2007)
  113. Mueller, R. D., Yasuda, H., Hatch, C. L., Bonner, W. M. & Bradbury, E. M. Identification of ubiquitinated histones 2A and 2B in Physarum polycephalum. Disappearance of these proteins at metaphase and reappearance at anaphase. J. Biol. Chem. 260, 5147–5153 (1985). (10.1016/S0021-9258(18)89191-8) / J. Biol. Chem. by RD Mueller (1985)
  114. Zhu, P. et al. A histone H2A deubiquitinase complex coordinating histone acetylation and H1 dissociation in transcriptional regulation. Mol. Cell 27, 609–621 (2007). (10.1016/j.molcel.2007.07.024) / Mol. Cell by P Zhu (2007)
  115. Joo, H. Y. et al. Regulation of cell cycle progression and gene expression by H2A deubiquitination. Nature 449, 1068–1072 (2007). (10.1038/nature06256) / Nature by HY Joo (2007)
  116. Nicassio, F. et al. Human USP3 is a chromatin modifier required for S phase progression and genome stability. Curr. Biol. 22, 1972–1977 (2007). (10.1016/j.cub.2007.10.034) / Curr. Biol. by F Nicassio (2007)
  117. Zhang, X. Y. et al. The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Mol. Cell 29, 102–111 (2008). (10.1016/j.molcel.2007.12.015) / Mol. Cell by XY Zhang (2008)
  118. Nijman, S. M. et al. The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Mol. Cell 17, 331–339 (2005). A nice example of the application of an siRNA library screen to identify USP1 as a regulator of FANCD2. (10.1016/j.molcel.2005.01.008) / Mol. Cell by SM Nijman (2005)
  119. Oestergaard, V. H. et al. Deubiquitination of FANCD2 is required for DNA crosslink repair. Mol. Cell 28, 798–809 (2007). (10.1016/j.molcel.2007.09.020) / Mol. Cell by VH Oestergaard (2007)
  120. Chiu, Y. H., Zhao, M. & Chen, Z. J. Ubiquitin in NF-κB signaling. Chem. Rev. 4, 1549–1560 (2009). (10.1021/cr800554j) / Chem. Rev. by YH Chiu (2009)
  121. Sun, S. C. Deubiquitylation and regulation of the immune response. Nature Rev. Immunol. 8, 501–511 (2008). (10.1038/nri2337) / Nature Rev. Immunol. by SC Sun (2008)
  122. Boone, D. L. et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nature Immunol. 5, 1052–1060 (2004). (10.1038/ni1110) / Nature Immunol. by DL Boone (2004)
  123. Lee, E. G. et al. Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science 289, 2350–2354 (2000). (10.1126/science.289.5488.2350) / Science by EG Lee (2000)
  124. Compagno, M. et al. Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma. Nature 459, 717–721 (2009). (10.1038/nature07968) / Nature by M Compagno (2009)
  125. Kato, M. et al. Frequent inactivation of A20 in B-cell lymphomas. Nature 459, 712–716 (2009). (10.1038/nature07969) / Nature by M Kato (2009)
  126. Schmitz, R. et al. TNFAIP3 (A20) is a tumor suppressor gene in Hodgkin lymphoma and primary mediastinal B cell lymphoma. J. Exp. Med. 5, 981–989 (2009). (10.1084/jem.20090528) / J. Exp. Med. by R Schmitz (2009)
  127. Wertz, I. E. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-κB signalling. Nature 430, 694–699 (2004). First description of ubiquitin chain editing by a DUB. (10.1038/nature02794) / Nature by IE Wertz (2004)
  128. Shembade, N. et al. The E3 ligase Itch negatively regulates inflammatory signaling pathways by controlling the function of the ubiquitin-editing enzyme A20. Nature Immunol. 9, 254–262 (2008). (10.1038/ni1563) / Nature Immunol. by N Shembade (2008)
  129. Shembade, N., Parvatiyar, K., Harhaj, N. S. & Harhaj, E. W. The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-κB signalling. EMBO J. 5, 513–522 (2009). (10.1038/emboj.2008.285) / EMBO J. by N Shembade (2009)
  130. Enesa, K. et al. NF-κB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling. J. Biol. Chem. 283, 7036–7045 (2008). (10.1074/jbc.M708690200) / J. Biol. Chem. by K Enesa (2008)
  131. Dupont, S. et al. FAM/USP9x, a deubiquitinating enzyme essential for TGFβ signaling, controls Smad4 monoubiquitination. Cell 136, 123–135 (2009). (10.1016/j.cell.2008.10.051) / Cell by S Dupont (2009)
  132. Burrows, J. F. et al. USP17 regulates Ras activation and cell proliferation by blocking RCE 1 activity. J. Biol. Chem. 14, 9587–9595 (2009). (10.1074/jbc.M807216200) / J. Biol. Chem. by JF Burrows (2009)
  133. Rigden, D. J., Liu, H., Hayes, S. D., Urbé, S. & Clague, M. J. Ab initio protein modelling reveals novel human MIT domains. FEBS Lett. 583, 872–878 (2009). (10.1016/j.febslet.2009.02.012) / FEBS Lett. by DJ Rigden (2009)
  134. Burrows, J. F., McGrattan, M. J. & Johnston, J. A. The DUB/USP17 deubiquitinating enzymes, a multigene family within a tandemly repeated sequence. Genomics 85, 524–529 (2005). (10.1016/j.ygeno.2004.11.013) / Genomics by JF Burrows (2005)
  135. Quesada, V. et al. Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases. Biochem. Biophys. Res. Commun. 314, 54–62 (2004). (10.1016/j.bbrc.2003.12.050) / Biochem. Biophys. Res. Commun. by V Quesada (2004)
  136. Pena, V., Liu, S., Bujnicki, J. M., Luhrmann, R. & Wahl, M. C. Structure of a multipartite protein-protein interaction domain in splicing factor prp8 and its link to retinitis pigmentosa. Mol. Cell 25, 615–624 (2007). (10.1016/j.molcel.2007.01.023) / Mol. Cell by V Pena (2007)
  137. Misaghi, S. et al. Structure of the ubiquitin hydrolase UCH-L3 complexed with a suicide substrate. J. Biol. Chem. 280, 1512–1520 (2005). (10.1074/jbc.M410770200) / J. Biol. Chem. by S Misaghi (2005)
  138. Ye, Y., Scheel, H., Hofmann, K. & Komander, D. Dissection of USP catalytic domains reveals five common insertion points. Mol. Biosyst. 17 Jul 2009 (doi:10.1039/b907669g)
Dates
Type When
Created 16 years, 1 month ago (July 23, 2009, 7:27 a.m.)
Deposited 2 years, 3 months ago (May 25, 2023, 11:25 p.m.)
Indexed 0 minutes ago (Aug. 29, 2025, 2:40 a.m.)
Issued 16 years ago (Aug. 1, 2009)
Published 16 years ago (Aug. 1, 2009)
Published Print 16 years ago (Aug. 1, 2009)
Funders 0

None

@article{Komander_2009, title={Breaking the chains: structure and function of the deubiquitinases}, volume={10}, ISSN={1471-0080}, url={http://dx.doi.org/10.1038/nrm2731}, DOI={10.1038/nrm2731}, number={8}, journal={Nature Reviews Molecular Cell Biology}, publisher={Springer Science and Business Media LLC}, author={Komander, David and Clague, Michael J. and Urbé, Sylvie}, year={2009}, month=aug, pages={550–563} }