Ubiquitylation as a rheostat for TCR signaling: From targeted approaches toward global profiling

Frontiers in Immunology

Volumn 6, Issue DEC, 2015, Pages

  O'Leary, Claire E ^a   Lewis, Emma L ^a   Oliver, Paula M ^a  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Proteomics; T cell; TCR signaling; Ubiquitin; Ubiquitin protein ligases

Indexed keywords

ALPHA INTERFERON RECEPTOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR FOXP3; TRANSCRIPTION FACTOR NFAT; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UBIQUITIN PROTEIN LIGASE E3; UBIQUITIN PROTEIN LIGASE NEDD4;

APOPTOSIS; CELL PROLIFERATION; DNA REPAIR; DOWN REGULATION; ENZYME ACTIVITY; HUMAN; IMMUNE RESPONSE; IMMUNOPRECIPITATION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; PHENOTYPE; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; REVIEW; SIGNAL TRANSDUCTION; UBIQUITINATION;

EID: 84954233285     PISSN: None     EISSN: 16643224     Source Type: Journal    
DOI: 10.3389/fimmu.2015.00618     Document Type: Review

References (201)

1. Curtsinger JM, Mescher MF. Inflammatory cytokines as a third signal for T cell activation. Curr Opin Immunol (2010) 22:333-40. doi: 10.1016/j.coi.2010.02.013.
2. O'Shea JJ, Paul WE. Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science (2010) 327:1098-102. doi:10.1126/science.1178334.
3. Hubo M, Trinschek B, Kryczanowsky F, Tuettenberg A, Steinbrink K, Jonuleit H. Costimulatory molecules on immunogenic versus tolerogenic human dendritic cells. Front Immunol (2013) 4:82. doi:10.3389/fimmu.2013.00082.
4. Tubo NJ, Jenkins MK. TCR signal quantity and quality in CD4 T cell differentiation. Trends Immunol (2014) 35:591-6. doi:10.1016/j.it.2014.09.008.
5. Benczik M, Gaffen SL. The interleukin (IL)-2 family cytokines: survival and proliferation signaling pathways in T lymphocytes. Immunol Invest (2004) 33:109-42. doi:10.1081/IMM-120030732.
6. Brownlie RJ, Zamoyska R. T cell receptor signalling networks: branched, diversified and bounded. Nat Rev Immunol (2013) 13:257-69. doi:10.1038/nri3403.
7. Zikherman J, Au-Yeung B. The role of T cell receptor signaling thresholds in guiding T cell fate decisions. Curr Opin Immunol (2015) 33:43-8. doi:10.1016/j.coi.2015.01.012.
8. Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans (2009) 37:937-53. doi:10.1042/bst0370937.
9. Kulathu Y, Komander D. Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages. Nat Rev Mol Cell Biol (2012) 13:508-23. doi:10.1038/nrm3394.
10. Friend SF, Deason-Towne F, Peterson LK, Berger AJ, Dragone LL. Regulation of T cell receptor complex-mediated signaling by ubiquitin and ubiquitin-like modifications. Am J Clin Exp Immunol (2014) 3:107-23.
11. Park Y, Jin HS, Aki D, Lee J, Liu YC. The ubiquitin system in immune regulation. Adv Immunol (2014) 124:17-66. doi:10.1016/b978-0-12-800147-9.00002-9.
12. Clague MJ, Heride C, Urbe S. The demographics of the ubiquitin system. Trends Cell Biol (2015) 25(7):417-26. doi:10.1016/j.tcb.2015.03.002.
13. Ardley HC, Robinson PA. E3 ubiquitin ligases. Essays Biochem (2005) 41:15-30. doi:10.1042/eb0410015.
14. Rotin D, Kumar S. Physiological functions of the HECT family of ubiquitin ligases. Nat Rev Mol Cell Biol (2009) 10:398-409. doi:10.1038/nrm2690.
15. Wenzel DM, Lissounov A, Brzovic PS, Klevit RE. UBCH7 reactivity profile reveals Parkin and HHARI to be RING/HECT hybrids. Nature (2011) 474:105-8. doi:10.1038/nature09966.
16. Dikic I, Wakatsuki S, Walters KJ. Ubiquitin-binding domains - from structures to functions. Nat Rev Mol Cell Biol (2009) 10:659-71. doi:10.1038/nrm2767.
17. Iwai K, Tokunaga F. Linear polyubiquitination: a new regulator of NF-kappaB activation. EMBO Rep (2009) 10:706-13. doi:10.1038/embor.2009.144.
18. Xu P, Duong DM, Seyfried NT, Cheng D, Xie Y, Robert J, et al. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell (2009) 137:133-45. doi:10.1016/j.cell.2009.01.041.
19. Komander D, Rape M. The ubiquitin code. Annu Rev Biochem (2012) 81:203-29. doi:10.1146/annurev-biochem-060310-170328.
20. Komander D, Clague MJ, Urbe S. Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol (2009) 10:550-63. doi:10.1038/nrm2731.
21. Monia BP, Ecker DJ, Jonnalagadda S, Marsh J, Gotlib L, Butt TR, et al. Gene synthesis, expression, and processing of human ubiquitin carboxyl extension proteins. J Biol Chem (1989) 264:4093-103.
22. Brockmeyer C, Paster W, Pepper D, Tan CP, Trudgian DC, McGowan S, et al. T cell receptor (TCR)-induced tyrosine phosphorylation dynamics identifies THEMIS as a new TCR signalosome component. J Biol Chem (2011) 286:7535-47. doi:10.1074/jbc.M110.201236.
23. Navarro MN, Goebel J, Feijoo-Carnero C, Morrice N, Cantrell DA. Phosphoproteomic analysis reveals an intrinsic pathway for the regulation of histone deacetylase 7 that controls the function of cytotoxic T lymphocytes. Nat Immunol (2011) 12:352-61. doi:10.1038/ni.2008.
24. Salek M, McGowan S, Trudgian DC, Dushek O, de Wet B, Efstathiou G, et al. Quantitative phosphoproteome analysis unveils LAT as a modulator of CD3zeta and ZAP-70 tyrosine phosphorylation. PLoS One (2013) 8:e77423. doi:10.1371/journal.pone.0077423.
25. Chylek LA, Akimov V, Dengjel J, Rigbolt KT, Hu B, Hlavacek WS, et al. Phosphorylation site dynamics of early T-cell receptor signaling. PLoS One (2014) 9:e104240. doi:10.1371/journal.pone.0104240.
26. Navarro MN, Goebel J, Hukelmann JL, Cantrell DA. Quantitative phosphoproteomics of cytotoxic T cells to reveal protein kinase d 2 regulated networks. Mol Cell Proteomics (2014) 13:3544-57. doi:10.1074/mcp.M113.037242.
27. Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, et al. Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol (2014) 15:384-92. doi:10.1038/ni.2843.
28. Ji Q, Ding Y, Salomon AR. SRC homology 2 domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) N-terminal tyrosine residues regulate a dynamic signaling equilibrium involving feedback of proximal T-cell receptor (TCR) signaling. Mol Cell Proteomics (2015) 14:30-40. doi:10.1074/mcp.M114.037861.
29. Bachmaier K, Krawczyk C, Kozieradzki I, Kong YY, Sasaki T, Oliveira-dos-Santos A, et al. Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature (2000) 403:211-6. doi:10.1038/35003228.
30. Chiang YJ, Kole HK, Brown K, Naramura M, Fukuhara S, Hu RJ, et al. Cbl-b regulates the CD28 dependence of T-cell activation. Nature (2000) 403:216-20. doi:10.1038/35003235.
31. Joazeiro CA, Wing SS, Huang H, Leverson JD, Hunter T, Liu YC. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2-dependent ubiquitin-protein ligase. Science (1999) 286:309-12. doi:10.1126/science.286.5438.309.
32. Zheng N, Wang P, Jeffrey PD, Pavletich NP. Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases. Cell (2000) 102:533-9. doi:10.1016/S0092-8674(00)00057-X.
33. Schmidt MH, Dikic I. The Cbl interactome and its functions. Nat Rev Mol Cell Biol (2005) 6:907-18. doi:10.1038/nrm1762.
34. Staub O, Rotin D. Role of ubiquitylation in cellular membrane transport. Physiol Rev (2006) 86:669-707. doi:10.1152/physrev.00020.2005.
35. Liu YC, Gu H. Cbl and Cbl-b in T-cell regulation. Trends Immunol (2002) 23:140-3. doi:10.1016/S1471-4906(01)02157-3.
36. Jeon MS, Atfield A, Venuprasad K, Krawczyk C, Sarao R, Elly C, et al. Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity (2004) 21:167-77. doi:10.1016/j.immuni.2004.07.013.
37. Heissmeyer V, Macian F, Im SH, Varma R, Feske S, Venuprasad K, et al. Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat Immunol (2004) 5:255-65. doi:10.1038/ni1047.
38. Fang D, Liu YC. Proteolysis-independent regulation of PI3K by Cbl-b-mediated ubiquitination in T cells. Nat Immunol (2001) 2:870-5. doi:10.1038/ni0901-870.
39. Fang D, Wang HY, Fang N, Altman Y, Elly C, Liu YC. Cbl-b, a RING-type E3 ubiquitin ligase, targets phosphatidylinositol 3-kinase for ubiquitination in T cells. J Biol Chem (2001) 276:4872-8. doi:10.1074/jbc.M008901200.
40. Yasuda T, Tezuka T, Maeda A, Inazu T, Yamanashi Y, Gu H, et al. Cbl-b positively regulates Btk-mediated activation of phospholipase C-gamma2 in B cells. J Exp Med (2002) 196:51-63. doi:10.1084/jem.20020068.
41. Liu Q, Zhou H, Langdon WY, Zhang J. E3 ubiquitin ligase Cbl-b in innate and adaptive immunity. Cell Cycle (2014) 13:1875-84. doi:10.4161/cc.29213.
42. Naramura M, Kole HK, Hu RJ, Gu H. Altered thymic positive selection and intracellular signals in Cbl-deficient mice. Proc Natl Acad Sci U S A (1998) 95:15547-52. doi:10.1073/pnas.95.26.15547.
43. Thien CB, Langdon WY. c-Cbl: a regulator of T cell receptor-mediated signalling. Immunol Cell Biol (1998) 76:473-82. doi:10.1046/j.1440-1711.1998.00768.x.
44. Wang HY, Altman Y, Fang D, Elly C, Dai Y, Shao Y, et al. Cbl promotes ubiquitination of the T cell receptor zeta through an adaptor function of Zap-70. J Biol Chem (2001) 276:26004-11. doi:10.1074/jbc.M010738200.
45. Kadlecek TA, van Oers NS, Lefrancois L, Olson S, Finlay D, Chu DH, et al. Differential requirements for ZAP-70 in TCR signaling and T cell development. J Immunol (1998) 161:4688-94.
46. Myers MD, Sosinowski T, Dragone LL, White C, Band H, Gu H, et al. Src-like adaptor protein regulates TCR expression on thymocytes by linking the ubiquitin ligase c-Cbl to the TCR complex. Nat Immunol (2006) 7:57-66. doi:10.1038/ni1291.
47. Tang J, Sawasdikosol S, Chang JH, Burakoff SJ. SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling. Proc Natl Acad Sci U S A (1999) 96:9775-80. doi:10.1073/pnas.96.17.9775.
48. Sosinowski T, Pandey A, Dixit VM, Weiss A. Src-like adaptor protein (SLAP) is a negative regulator of T cell receptor signaling. J Exp Med (2000) 191:463-74. doi:10.1084/jem.191.3.463.
49. Sosinowski T, Killeen N, Weiss A. The Src-like adaptor protein downregulates the T cell receptor on CD4+CD8+ thymocytes and regulates positive selection. Immunity (2001) 15:457-66. doi:10.1016/S1074-7613(01)00195-9.
50. Myers MD, Dragone LL, Weiss A. Src-like adaptor protein down-regulates T cell receptor (TCR)-CD3 expression by targeting TCRzeta for degradation. J Cell Biol (2005) 170:285-94. doi:10.1083/jcb.200501164.
51. Dragone LL, Shaw LA, Myers MD, Weiss A. SLAP, a regulator of immunoreceptor ubiquitination, signaling, and trafficking. Immunol Rev (2009) 232:218-28. doi:10.1111/j.1600-065X.2009.00827.x.
52. Ouchida R, Yamasaki S, Hikida M, Masuda K, Kawamura K, Wada A, et al. A lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3zeta-chain degradation. Immunity (2008) 29:33-43. doi:10.1016/j.immuni.2008.04.024.
53. Kawai Y, Ouchida R, Yamasaki S, Dragone L, Tsubata T, Wang JY. LAPTM5 promotes lysosomal degradation of intracellular CD3zeta but not of cell surface CD3zeta. Immunol Cell Biol (2014) 92:527-34. doi:10.1038/icb.2014.18.
54. Watanabe Y, Sasahara Y, Ramesh N, Massaad MJ, Yeng Looi C, Kumaki S, et al. T-cell receptor ligation causes Wiskott-Aldrich syndrome protein degradation and F-actin assembly downregulation. J Allergy Clin Immunol (2013) 132:648.e-55.e. doi:10.1016/j.jaci.2013.03.046.
55. Thien CB, Dagger SA, Steer JH, Koentgen F, Jansen ES, Scott CL, et al. c-Cbl promotes T cell receptor-induced thymocyte apoptosis by activating the phosphatidylinositol 3-kinase/Akt pathway. J Biol Chem (2010) 285:10969-81. doi:10.1074/jbc.M109.094920.
56. Roa NS, Ordonez-Rueda D, Chavez-Rios JR, Raman C, Garcia-Zepeda EA, Lozano F, et al. The carboxy-terminal region of CD5 is required for c-CBL mediated TCR signaling downmodulation in thymocytes. Biochem Biophys Res Commun (2013) 432:52-9. doi:10.1016/j.bbrc.2013.01.086.
57. Naramura M, Jang IK, Kole H, Huang F, Haines D, Gu H. c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation. Nat Immunol (2002) 3:1192-9. doi:10.1038/ni855.
58. Magnifico A, Ettenberg S, Yang C, Mariano J, Tiwari S, Fang S, et al. WW domain HECT E3s target Cbl RING finger E3s for proteasomal degradation. J Biol Chem (2003) 278:43169-77. doi:10.1074/jbc.M308009200.
59. Yang B, Gay DL, MacLeod MK, Cao X, Hala T, Sweezer EM, et al. Nedd4 augments the adaptive immune response by promoting ubiquitin-mediated degradation of Cbl-b in activated T cells. Nat Immunol (2008) 9:1356-63. doi:10.1038/ni.1670.
60. Zhao Y, Guo H, Qiao G, Zucker M, Langdon WY, Zhang J. E3 ubiquitin ligase Cbl-b regulates thymic-derived CD4+CD25+ regulatory T cell development by targeting Foxp3 for ubiquitination. J Immunol (2015) 194:1639-45. doi:10.4049/jimmunol.1402434.
61. Huibregtse JM, Scheffner M, Beaudenon S, Howley PM. A family of proteins structurally and functionally related to the E6-AP ubiquitin-protein ligase. Proc Natl Acad Sci U S A (1995) 92:2563-7. doi:10.1073/pnas.92.11.5249-a.
62. Gay DL, Ramon H, Oliver PM. Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity. Immunol Res (2008) 42:51-64. doi:10.1007/s12026-008-8034-0.
63. Yang B, Kumar S. Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions. Cell Death Differ (2010) 17:68-77. doi:10.1038/cdd.2009.84.
64. Staub O, Dho S, Henry P, Correa J, Ishikawa T, McGlade J, et al. WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome. EMBO J (1996) 15:2371-80.
65. Kamynina E, Debonneville C, Bens M, Vandewalle A, Staub O. A novel mouse Nedd4 protein suppresses the activity of the epithelial Na+ channel. FASEB J (2001) 15:204-14. doi:10.1096/fj.00-0191com.
66. Henry PC, Kanelis V, O'Brien MC, Kim B, Gautschi I, Forman-Kay J, et al. Affinity and specificity of interactions between Nedd4 isoforms and the epithelial Na+ channel. J Biol Chem (2003) 278:20019-28. doi:10.1074/jbc.M211153200.
67. Snyder PM, Steines JC, Olson DR. Relative contribution of Nedd4 and Nedd4-2 to ENaC regulation in epithelia determined by RNA interference. J Biol Chem (2004) 279:5042-6. doi:10.1074/jbc.M312477200.
68. Fouladkou F, Landry T, Kawabe H, Neeb A, Lu C, Brose N, et al. The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proc Natl Acad Sci U S A (2008) 105:8585-90. doi:10.1073/pnas.0803233105.
69. Maddika S, Kavela S, Rani N, Palicharla VR, Pokorny JL, Sarkaria JN, et al. WWP2 is an E3 ubiquitin ligase for PTEN. Nat Cell Biol (2011) 13:728-33. doi:10.1038/ncb2240.
70. Guo H, Qiao G, Ying H, Li Z, Zhao Y, Liang Y, et al. E3 ubiquitin ligase Cbl-b regulates Pten via Nedd4 in T cells independently of its ubiquitin ligase activity. Cell Rep (2012) 1:472-82. doi:10.1016/j.celrep.2012.04.008.
71. Scharschmidt E, Wegener E, Heissmeyer V, Rao A, Krappmann D. Degradation of Bcl10 induced by T-cell activation negatively regulates NF-kappa B signaling. Mol Cell Biol (2004) 24:3860-73. doi:10.1128/MCB.24.9.3860-3873.2004.
72. Kimura T, Kawabe H, Jiang C, Zhang W, Xiang YY, Lu C, et al. Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease. Proc Natl Acad Sci U S A (2011) 108:3216-21. doi:10.1073/pnas.1010334108.
73. Heikamp EB, Patel CH, Collins S, Waickman A, Oh MH, Sun IH, et al. The AGC kinase SGK1 regulates TH1 and TH2 differentiation downstream of the mTORC2 complex. Nat Immunol (2014) 15:457-64. doi:10.1038/ni.2867.
74. Chen A, Gao B, Zhang J, McEwen T, Ye SQ, Zhang D, et al. The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination. Mol Cell Biol (2009) 29:5348-56. doi:10.1128/mcb.00407-09.
75. Perry WL, Hustad CM, Swing DA, O'Sullivan TN, Jenkins NA, Copeland NG. The itchy locus encodes a novel ubiquitin protein ligase that is disrupted in a18H mice. Nat Genet (1998) 18:143-6. doi:10.1038/ng0298-143.
76. Fang D, Elly C, Gao B, Fang N, Altman Y, Joazeiro C, et al. Dysregulation of T lymphocyte function in itchy mice: a role for itch in TH2 differentiation. Nat Immunol (2002) 3:281-7. doi:10.1038/ni763.
77. Oliver PM, Cao X, Worthen GS, Shi P, Briones N, MacLeod M, et al. Ndfip1 protein promotes the function of itch ubiquitin ligase to prevent T cell activation and T helper 2 cell-mediated inflammation. Immunity (2006) 25:929-40. doi:10.1016/j.immuni.2006.10.012.
78. Qiu L, Joazeiro C, Fang N, Wang HY, Elly C, Altman Y, et al. Recognition and ubiquitination of Notch by itch, a hect-type E3 ubiquitin ligase. J Biol Chem (2000) 275:35734-7. doi:10.1074/jbc.M007300200.
79. Matesic LE, Copeland NG, Jenkins NA. Itchy mice: the identification of a new pathway for the development of autoimmunity. Curr Top Microbiol Immunol (2008) 321:185-200. doi:10.1007/978-3-540-75203-5_9.
80. Aki D, Liu YC. To go or not to go: the "itchy" effect on the destiny of hematopoietic stem cells. Cell Res (2011) 21:1161-3. doi:10.1038/cr.2011.95.
81. Rathinam C, Matesic LE, Flavell RA. The E3 ligase itch is a negative regulator of the homeostasis and function of hematopoietic stem cells. Nat Immunol (2011) 12:399-407. doi:10.1038/ni.2021.
82. Xiao N, Eto D, Elly C, Peng G, Crotty S, Liu YC. The E3 ubiquitin ligase Itch is required for the differentiation of follicular helper T cells. Nat Immunol (2014) 15:657-66. doi:10.1038/ni.2912.
83. Lohr NJ, Molleston JP, Strauss KA, Torres-Martinez W, Sherman EA, Squires RH, et al. Human ITCH E3 ubiquitin ligase deficiency causes syndromic multisystem autoimmune disease. Am J Hum Genet (2010) 86:447-53. doi:10.1016/j.ajhg.2010.01.028.
84. Meroni G, Diez-Roux G. TRIM/RBCC, a novel class of 'single protein RING finger' E3 ubiquitin ligases. Bioessays (2005) 27:1147-57. doi:10.1002/bies.20304.
85. Micale L, Chaignat E, Fusco C, Reymond A, Merla G. The tripartite motif: structure and function. Adv Exp Med Biol (2012) 770:11-25. doi:10.1007/978-1-4614-5398-7_2.
86. Reymond A, Meroni G, Fantozzi A, Merla G, Cairo S, Luzi L, et al. The tripartite motif family identifies cell compartments. EMBO J (2001) 20:2140-51. doi:10.1093/emboj/20.9.2140.
87. Napolitano LM, Meroni G. TRIM family: pleiotropy and diversification through homomultimer and heteromultimer formation. IUBMB Life (2012) 64:64-71. doi:10.1002/iub.580.
88. Sardiello M, Cairo S, Fontanella B, Ballabio A, Meroni G. Genomic analysis of the TRIM family reveals two groups of genes with distinct evolutionary properties. BMC Evol Biol (2008) 8:225. doi:10.1186/1471-2148-8-225.
89. Marin I. Origin and diversification of TRIM ubiquitin ligases. PLoS One (2012) 7:e50030. doi:10.1371/journal.pone.0050030.
90. Zou W, Zhang DE. The interferon-inducible ubiquitin-protein isopeptide ligase (E3) EFP also functions as an ISG15 E3 ligase. J Biol Chem (2006) 281:3989-94. doi:10.1074/jbc.M510787200.
91. Chu Y, Yang X. SUMO E3 ligase activity of TRIM proteins. Oncogene (2011) 30:1108-16. doi:10.1038/onc.2010.462.
92. Napolitano LM, Jaffray EG, Hay RT, Meroni G. Functional interactions between ubiquitin E2 enzymes and TRIM proteins. Biochem J (2011) 434:309-19. doi:10.1042/bj20101487.
93. Gack MU, Shin YC, Joo CH, Urano T, Liang C, Sun L, et al. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature (2007) 446:916-20. doi:10.1038/nature05732.
94. Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity (2010) 33:765-76. doi:10.1016/j.immuni.2010.10.013.
95. Shen Y, Li NL, Wang J, Liu B, Lester S, Li K. TRIM56 is an essential component of the TLR3 antiviral signaling pathway. J Biol Chem (2012) 287:36404-13. doi:10.1074/jbc.M112.397075.
96. Zhao W, Wang L, Zhang M, Wang P, Yuan C, Qi J, et al. Tripartite motif-containing protein 38 negatively regulates TLR3/4- and RIG-I-mediated IFN-beta production and antiviral response by targeting NAP1. J Immunol (2012) 188:5311-8. doi:10.4049/jimmunol.1103506.
97. Zhao W, Wang L, Zhang M, Yuan C, Gao C. E3 ubiquitin ligase tripartite motif 38 negatively regulates TLR-mediated immune responses by proteasomal degradation of TNF receptor-associated factor 6 in macrophages. J Immunol (2012) 188:2567-74. doi:10.4049/jimmunol.1103255.
98. Zurek B, Schoultz I, Neerincx A, Napolitano LM, Birkner K, Bennek E, et al. TRIM27 negatively regulates NOD2 by ubiquitination and proteasomal degradation. PLoS One (2012) 7:e41255. doi:10.1371/journal.pone.0041255.
99. Qiu H, Huang F, Xiao H, Sun B, Yang R. TRIM22 inhibits the TRAF6-stimulated NF-kappaB pathway by targeting TAB2 for degradation. Virol Sin (2013) 28:209-15. doi:10.1007/s12250-013-3343-4.
100. Narayan K, Waggoner L, Pham ST, Hendricks GL, Waggoner SN, Conlon J, et al. TRIM13 is a negative regulator of MDA5-mediated type I interferon production. J Virol (2014) 88:10748-57. doi:10.1128/jvi.02593-13.
101. Rajsbaum R, Versteeg GA, Schmid S, Maestre AM, Belicha-Villanueva A, Martinez-Romero C, et al. Unanchored K48-linked polyubiquitin synthesized by the E3-ubiquitin ligase TRIM6 stimulates the interferon-IKKepsilon kinase-mediated antiviral response. Immunity (2014) 40:880-95. doi:10.1016/j.immuni.2014.04.018.
102. Weng L, Mitoma H, Trichot C, Bao M, Liu Y, Zhang Z, et al. The E3 ubiquitin ligase tripartite motif 33 is essential for cytosolic RNA-induced NLRP3 inflammasome activation. J Immunol (2014) 193:3676-82. doi:10.4049/jimmunol.1401448.
103. Wynne C, Lazzari E, Smith S, McCarthy EM, Ni Gabhann J, Kallal LE, et al. TRIM68 negatively regulates IFN-beta production by degrading TRK fused gene, a novel driver of IFN-beta downstream of anti-viral detection systems. PLoS One (2014) 9:e101503. doi:10.1371/journal.pone.0101503.
104. Ozato K, Shin DM, Chang TH, Morse HC III. TRIM family proteins and their emerging roles in innate immunity. Nat Rev Immunol (2008) 8:849-60. doi:10.1038/nri2413.
105. Versteeg GA, Rajsbaum R, Sanchez-Aparicio MT, Maestre AM, Valdiviezo J, Shi M, et al. The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors. Immunity (2013) 38:384-98. doi:10.1016/j.immuni.2012.11.013.
106. Rajsbaum R, Garcia-Sastre A, Versteeg GA. TRIMmunity: the roles of the TRIM E3-ubiquitin ligase family in innate antiviral immunity. J Mol Biol (2014) 426:1265-84. doi:10.1016/j.jmb.2013.12.005.
107. Tomar D, Singh R. TRIM family proteins: emerging class of RING E3 ligases as regulator of NF-kappaB pathway. Biol Cell (2015) 107:22-40. doi:10.1111/boc.201400046.
108. Chikuma S, Suita N, Okazaki IM, Shibayama S, Honjo T. TRIM28 prevents autoinflammatory T cell development in vivo. Nat Immunol (2012) 13:596-603. doi:10.1038/ni.2293.
109. Zhou XF, Yu J, Chang M, Zhang M, Zhou D, Cammas F, et al. TRIM28 mediates chromatin modifications at the TCRalpha enhancer and regulates the development of T and natural killer T cells. Proc Natl Acad Sci U S A (2012) 109:20083-8. doi:10.1073/pnas.1214704109.
110. Cai X, Srivastava S, Sun Y, Li Z, Wu H, Zuvela-Jelaska L, et al. Tripartite motif containing protein 27 negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II PI3K-C2beta. Proc Natl Acad Sci U S A (2011) 108:20072-7. doi:10.1073/pnas.1111233109.
111. Choi UY, Hur JY, Lee MS, Zhang Q, Choi WY, Kim LK, et al. Tripartite motif-containing protein 30 modulates TCR-activated proliferation and effector functions in CD4+ T cells. PLoS One (2014) 9:e95805. doi:10.1371/journal.pone.0095805.
112. Kong HJ, Anderson DE, Lee CH, Jang MK, Tamura T, Tailor P, et al. Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. J Immunol (2007) 179:26-30. doi:10.4049/jimmunol.179.1.26.
113. Yoshimi R, Chang TH, Wang H, Atsumi T, Morse HC III, Ozato K. Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-kappaB-dependent cytokine expression in fibroblasts. J Immunol (2009) 182:7527-38. doi:10.4049/jimmunol.0804121.
114. Higgs R, Lazzari E, Wynne C, Ni Gabhann J, Espinosa A, Wahren-Herlenius M, et al. Self protection from anti-viral responses - Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral toll-like receptors. PLoS One (2010) 5:e11776. doi:10.1371/journal.pone.0011776.
115. Espinosa A, Dardalhon V, Brauner S, Ambrosi A, Higgs R, Quintana FJ, et al. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med (2009) 206:1661-71. doi:10.1084/jem.20090585.
116. Rajsbaum R, Stoye JP, O'Garra A. Type I interferon-dependent and -independent expression of tripartite motif proteins in immune cells. Eur J Immunol (2008) 38:619-30. doi:10.1002/eji.200737916.
117. Zhao Y, Sun Y. Cullin-RING ligases as attractive anti-cancer targets. Curr Pharm Des (2013) 19:3215-25. doi:10.2174/13816128113199990300.
118. Zhou W, Wei W, Sun Y. Genetically engineered mouse models for functional studies of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases. Cell Res (2013) 23:599-619. doi:10.1038/cr.2013.44.
119. Bulatov E, Ciulli A. Targeting Cullin-RING E3 ubiquitin ligases for drug discovery: structure, assembly and small-molecule modulation. Biochem J (2015) 467:365-86. doi:10.1042/bj20141450.
120. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, et al. Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature (2002) 416:703-9. doi:10.1038/416703a.
121. Lydeard JR, Schulman BA, Harper JW. Building and remodelling Cullin-RING E3 ubiquitin ligases. EMBO Rep (2013) 14:1050-61. doi:10.1038/embor.2013.173.
122. Kawaida R, Yamada R, Kobayashi K, Tokuhiro S, Suzuki A, Kochi Y, et al. CUL1, a component of E3 ubiquitin ligase, alters lymphocyte signal transduction with possible effect on rheumatoid arthritis. Genes Immun (2005) 6:194-202. doi:10.1038/sj.gene.6364177.
123. Skaar JR, D'Angiolella V, Pagan JK, Pagano M. SnapShot: F box proteins II. Cell (2009) 137:1358,1358.e1351. doi:10.1016/j.cell.2009.05.040.
124. Fuchs SY, Chen A, Xiong Y, Pan ZQ, Ronai Z. HOS, a human homolog of slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene (1999) 18:2039-46. doi:10.1038/sj.onc.1202760.
125. Kumar KGS, Tang W, Ravindranath AK, Clark WA, Croze E, Fuchs SY. SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor. EMBO J (2003) 22:5480-90. doi:10.1093/emboj/cdg524.
126. Nakayama K, Hatakeyama S, Maruyama S-I, Kikuchi A, Onoé K, Good RA, et al. Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 gene. Proc Nat Acad Sci U S A (2003) 100:8752-7. doi:10.1073/pnas.1133216100.
127. Appleman LJ, Chernova I, LI L, Boussiotis VA. CD28 costimulation mediates transcription of SKP2 and CKS1, the substrate recognition components of SCFSkp2 ubiquitin ligase that leads p27kip1 to degradation. Cell Cycle (2014) 5:2123-9. doi:10.4161/cc.5.18.3139.
128. Mathew R, Seiler MP, Scanlon ST, Mao A-P, Constantinides MG, Bertozzi-Villa C, et al. BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs. Nature (2012) 491:618-21. doi:10.1038/nature11548.
129. Mathew R, Mao AP, Chiang AH, Bertozzi-Villa C, Bunker JJ, Scanlon ST, et al. A negative feedback loop mediated by the Bcl6-cullin 3 complex limits Tfh cell differentiation. J Exp Med (2014) 211:1137-51. doi:10.1084/jem.20132267.
130. Yen HC, Elledge SJ. Identification of SCF ubiquitin ligase substrates by global protein stability profiling. Science (2008) 322:923-9. doi:10.1126/science.1160462.
131. Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, et al. Global identification of modular cullin-RING ligase substrates. Cell (2011) 147:459-74. doi:10.1016/j.cell.2011.09.019.
132. Yumimoto K, Matsumoto M, Oyamada K, Moroishi T, Nakayama KI. Comprehensive identification of substrates for F-box proteins by differential proteomics analysis. J Proteome Res (2012) 11:3175-85. doi:10.1021/pr201216u.
133. Yoshida Y, Saeki Y, Murakami A, Kawawaki J, Tsuchiya H, Yoshihara H, et al. A comprehensive method for detecting ubiquitinated substrates using TR-TUBE. Proc Natl Acad Sci U S A (2015) 112:4630-5. doi:10.1073/pnas.1422313112.
134. Lin JT, Lineberry NB, Kattah MG, Su LL, Utz PJ, Fathman CG, et al. Naive CD4 t cell proliferation is controlled by mammalian target of rapamycin regulation of GRAIL expression. J Immunol (2009) 182:5919-28. doi:10.4049/jimmunol.0803986.
135. Anandasabapathy N, Ford GS, Bloom D, Holness C, Paragas V, Seroogy C, et al. GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4(+) T cells. Immunity (2003) 18:535-47. doi:10.1016/S1074-7613(03)00084-0.
136. Schartner JM, Simonson WT, Wernimont SA, Nettenstrom LM, Huttenlocher A, Seroogy CM. Gene related to anergy in lymphocytes (GRAIL) expression in CD4+ T cells impairs actin cytoskeletal organization during T cell/antigen-presenting cell interactions. J Biol Chem (2009) 284:34674-81. doi:10.1074/jbc.M109.024497.
137. Kriegel MA, Rathinam C, Flavell RA. E3 ubiquitin ligase GRAIL controls primary T cell activation and oral tolerance. Proc Natl Acad Sci U S A (2009) 106:16770-5. doi:10.1073/pnas.0908957106.
138. Nurieva RI, Zheng S, Jin W, Chung Y, Zhang Y, Martinez GJ, et al. The E3 ubiquitin ligase GRAIL regulates T cell tolerance and regulatory T cell function by mediating T cell receptor-CD3 degradation. Immunity (2010) 32:670-80. doi:10.1016/j.immuni.2010.05.002.
139. Chang M, Jin W, Chang J-H, Xiao Y, Brittain GC, Yu J, et al. The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity. Nat Immunol (2011) 12:1002-9. doi:10.1038/ni.2090.
140. McDonough H, Patterson C. CHIP: a link between the chaperone and proteasome systems. Cell Stress Chaperones (2003) 8:303-8. doi:10.1379/1466-1268(2003)008<0303:CALBTC>2.0.CO;2.
141. Schulman BA, Chen ZJ. Protein ubiquitination: CHIPping away the symmetry. Mol Cell (2005) 20:653-5. doi:10.1016/j.molcel.2005.11.019.
142. Wang S, Li Y, Hu Y-H, Song R, Gao Y, Liu H-Y, et al. STUB1 is essential for T-cell activation by ubiquitinating CARMA1. Eur J Immunol (2013) 43:1034-41. doi:10.1002/eji.201242554.
143. Chen Z, Barbi J, Bu S, Yang H-Y, Li Z, Gao Y, et al. The ubiquitin ligase Stub1 negatively modulates regulatory T cell suppressive activity by promoting degradation of the transcription factor Foxp3. Immunity (2013) 39:272-85. doi:10.1016/j.immuni.2013.08.006.
144. Wei Q, Sha Y, Bhattacharya A, Abdel Fattah E, Bonilla D, Jyothula SS, et al. Regulation of IL-4 receptor signaling by STUB1 in lung inflammation. Am J Respir Crit Care Med (2014) 189:16-29. doi:10.1164/rccm.201305-0874OC.
145. Lee NK, Lee SY. Modulation of life and death by the tumor necrosis factor receptor-associated factors (TRAFs). J Biochem Mol Biol (2002) 35:61-6. doi:10.5483/BMBRep.2002.35.1.061.
146. Martinez-Forero I, Rouzaut A, Palazon A, Dubrot J, Melero I. Lysine 63 polyubiquitination in immunotherapy and in cancer-promoting inflammation. Clin Cancer Res (2009) 15:6751-7. doi:10.1158/1078-0432.ccr-09-1225.
147. Sun L, Deng L, Ea C-K, Xia Z-P, Chen ZJ. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell (2004) 14:289-301. doi:10.1038/nri1379.
148. Oeckinghaus A, Wegener E, Welteke V, Ferch U, Arslan SC, Ruland J, et al. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J (2007) 26:4634-45. doi:10.1038/sj.emboj.7601897.
149. Bidère N, Snow AL, Sakai K, Zheng L, Lenardo MJ. Caspase-8 regulation by direct interaction with TRAF6 in T cell receptor-induced NF-kappaB activation. Curr Biol (2006) 16:1666-71. doi:10.1016/j.cub.2006.06.062.
150. King CG, Kobayashi T, Cejas PJ, Kim T, Yoon K, Kim GK, et al. TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis. Nat Med (2006) 12:1088-92. doi:10.1038/nm1449.
151. King CG, Buckler JL, Kobayashi T, Hannah JR, Bassett G, Kim T, et al. Cutting edge: requirement for TRAF6 in the induction of T cell anergy. J Immunol (2008) 180:34-8. doi:10.4049/jimmunol.180.1.34.
152. So T, Choi H, Croft M. OX40 complexes with phosphoinositide 3-kinase and protein kinase B (PKB) to augment TCR-dependent PKB signaling. J Immunol (2011) 186:3547-55. doi:10.4049/jimmunol.1003156.
153. So T, Soroosh P, Eun S-Y, Altman A, Croft M. Antigen-independent signalosome of CARMA1, PKCθ, and TNF receptor-associated factor 2 (TRAF2) determines NF-κB signaling in T cells. Proc Natl Acad Sci U S A (2011) 108:2903-8. doi:10.1073/pnas.1008765108.
154. Tsitsikov EN, Laouini D, Dunn IF, Sannikova TY, Davidson L, Alt FW, et al. TRAF1 is a negative regulator of TNF signaling. Enhanced TNF signaling in TRAF1-deficient mice. Immunity (2001) 15:647-57. doi:10.1016/S1074-7613(01)00207-2.
155. Xie P, Kraus ZJ, Stunz LL, Liu Y, Bishop GA. TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling. J Immunol (2011) 186:143-55. doi:10.4049/jimmunol.1000290.
156. Yi Z, Stunz LL, Lin WW, Bishop GA. TRAF3 regulates homeostasis of CD8+ central memory T cells. PLoS One (2014) 9:e102120. doi:10.1371/journal.pone.0102120.
157. So T, Salek-Ardakani S, Nakano H, Ware CF, Croft M. TNF receptor-associated factor 5 limits the induction of Th2 immune responses. J Immunol (2004) 172:4292-7. doi:10.4049/jimmunol.172.7.4292.
158. Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, et al. A genomic and functional inventory of deubiquitinating enzymes. Cell (2005) 123:773-86. doi:10.1016/j.cell.2005.11.007.
159. Sowa ME, Bennett EJ, Gygi SP, Harper JW. Defining the human deubiquitinating enzyme interaction landscape. Cell (2009) 138:389-403. doi:10.1016/j.cell.2009.04.042.
160. Eletr ZM, Wilkinson KD. Regulation of proteolysis by human deubiquitinating enzymes. Biochim Biophys Acta (2014) 1843:114-28. doi:10.1016/j.bbamcr.2013.06.027.
161. Mouchantaf R, Azakir BA, McPherson PS, Millard SM, Wood SA, Angers A. The ubiquitin ligase itch is auto-ubiquitylated in vivo and in vitro but is protected from degradation by interacting with the deubiquitylating enzyme FAM/USP9X. J Biol Chem (2006) 281:38738-47. doi:10.1074/jbc.M605959200.
162. Park Y, Jin H-S, Liu Y-C. Regulation of T cell function by the ubiquitin-specific protease USP9X via modulating the Carma1-Bcl10-Malt1 complex. Proc Natl Acad Sci U S A (2013) 110:9433-8. doi:10.1073/pnas.1221925110.
163. Naik E, Webster JD, DeVoss J, Liu J, Suriben R, Dixit VM. Regulation of proximal T cell receptor signaling and tolerance induction by deubiquitinase Usp9X. J Exp Med (2014) 211:1947-55. doi:10.1084/jem.20140860.
164. Zou Q, Jin J, Hu H, Li HS, Romano S, Xiao Y, et al. USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nat Immunol (2014) 15:562-70. doi:10.1038/ni.2885.
165. van Loosdregt J, Fleskens V, Fu J, Brenkman AB, Bekker CP, Pals CE, et al. Stabilization of the transcription factor Foxp3 by the deubiquitinase USP7 increases Treg-cell-suppressive capacity. Immunity (2013) 39:259-71. doi:10.1016/j.immuni.2013.05.018.
166. Xie JJ, Liang JQ, Diao LH, Altman A, Li Y. TNFR-associated factor 6 regulates TCR signaling via interaction with and modification of LAT adapter. J Immunol (2013) 190:4027-36. doi:10.4049/jimmunol.1202742.
167. Shembade N, Ma A, Harhaj EW. Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin enzyme complexes. Science (2010) 327:1135-9. doi:10.1126/science.1182364.
168. Harhaj EW, Dixit VM. Regulation of NF-kappaB by deubiquitinases. Immunol Rev (2012) 246:107-24. doi:10.1111/j.1600-065X.2012.01100.x.
169. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, et al. Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science (2000) 289:2350-4. doi:10.1126/science.289.5488.2350.
170. Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature (2004) 430:694-9. doi:10.1038/nature02794.
171. Tewari M, Wolf FW, Seldin MF, O'Shea KS, Dixit VM, Turka LA. Lymphoid expression and regulation of A20, an inhibitor of programmed cell death. J Immunol (1995) 154:1699-706.
172. Duwel M, Welteke V, Oeckinghaus A, Baens M, Kloo B, Ferch U, et al. A20 negatively regulates T cell receptor signaling to NF-kappaB by cleaving Malt1 ubiquitin chains. J Immunol (2009) 182:7718-28. doi:10.4049/jimmunol.0803313.
173. De A, Dainichi T, Rathinam CV, Ghosh S. The deubiquitinase activity of A20 is dispensable for NF-kappaB signaling. EMBO Rep (2014) 15:775-83. doi:10.15252/embr.201338305.
174. Onizawa M, Oshima S, Schulze-Topphoff U, Oses-Prieto JA, Lu T, Tavares R, et al. The ubiquitin-modifying enzyme A20 restricts ubiquitination of the kinase RIPK3 and protects cells from necroptosis. Nat Immunol (2015) 16:618-27. doi:10.1038/ni.3172.
175. Kovalenko A, Chable-Bessia C, Cantarella G, Israel A, Wallach D, Courtois G. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature (2003) 424:801-5. doi:10.1038/nature01802.
176. Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G. CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature (2003) 424:793-6. doi:10.1038/nature01803.
177. Reiley WW, Jin W, Lee AJ, Wright A, Wu X, Tewalt EF, et al. Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses. J Exp Med (2007) 204:1475-85. doi:10.1084/jem.20062694.
178. Ahmed N, Zeng M, Sinha I, Polin L, Wei WZ, Rathinam C, et al. The E3 ligase itch and deubiquitinase cyld act together to regulate Tak1 and inflammation. Nat Immunol (2011) 12:1176-83. doi:10.1038/ni.2157.
179. Graessel A, Hauck SM, von Toerne C, Kloppmann E, Goldberg T, Koppensteiner H, et al. A combined omics approach to generate the surface atlas of human naive CD4+ T cells during early T-cell receptor activation. Mol Cell Proteomics (2015) 14:2085-102. doi:10.1074/mcp.M114.045690.
180. Pagani M, Rockstroh M, Schuster M, Rossetti G, Moro M, Crosti M, et al. Reference proteome of highly purified human Th1 cells reveals strong effects on metabolism and protein ubiquitination upon differentiation. Proteomics (2015) 15(21):3644-7. doi:10.1002/pmic.201400139.
181. Zanker D, Otto W, Chen W, von Bergen M, Tomm JM. Compartment resolved reference proteome map from highly purified naive, activated, effector, and memory CD8(+) murine immune cells. Proteomics (2015) 15:1808-12. doi:10.1002/pmic.201400405.
182. Seyfried NT, Xu P, Duong DM, Cheng D, Hanfelt J, Peng J. Systematic approach for validating the ubiquitinated proteome. Anal Chem (2008) 80:4161-9. doi:10.1021/ac702516a.
183. Peng J, Schwartz D, Elias JE, Thoreen CC, Cheng D, Marsischky G, et al. A proteomics approach to understanding protein ubiquitination. Nat Biotechnol (2003) 21:921-6. doi:10.1038/nbt849.
184. Meierhofer D, Wang X, Huang L, Kaiser P. Quantitative analysis of global ubiquitination in HeLa cells by mass spectrometry. J Proteome Res (2008) 7:4566-76. doi:10.1021/pr800468j.
185. Harper JW, Tan MK. Understanding cullin-RING E3 biology through proteomics-based substrate identification. Mol Cell Proteomics (2012) 11:1541-50. doi:10.1074/mcp.R112.021154.
186. Hjerpe R, Aillet F, Lopitz-Otsoa F, Lang V, England P, Rodriguez MS. Efficient protection and isolation of ubiquitylated proteins using tandem ubiquitin-binding entities. EMBO Rep (2009) 10:1250-8. doi:10.1038/embor.2009.192.
187. Lopitz-Otsoa F, Rodriguez MS, Aillet F. Properties of natural and artificial proteins displaying multiple ubiquitin-binding domains. Biochem Soc Trans (2010) 38:40-5. doi:10.1042/bst0380040.
188. Aillet F, Lopitz-Otsoa F, Hjerpe R, Torres-Ramos M, Lang V, Rodriguez MS. Isolation of ubiquitylated proteins using tandem ubiquitin-binding entities. Methods Mol Biol (2012) 832:173-83. doi:10.1007/978-1-61779-474-2_12.
189. Lopitz-Otsoa F, Rodriguez-Suarez E, Aillet F, Casado-Vela J, Lang V, Matthiesen R, et al. Integrative analysis of the ubiquitin proteome isolated using tandem ubiquitin binding entities (TUBEs). J Proteomics (2012) 75:2998-3014. doi:10.1016/j.jprot.2011.12.001.
190. Xu G, Paige JS, Jaffrey SR. Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling. Nat Biotechnol (2010) 28:868-73. doi:10.1038/nbt.1654.
191. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol Cell (2011) 44:325-40. doi:10.1016/j.molcel.2011.08.025.
192. Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, et al. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Mol Cell Proteomics (2011) 10:M111.013284. doi:10.1074/mcp.M111.013284.
193. Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, et al. Refined preparation and use of anti-diglycine remnant (K-epsilon-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments. Mol Cell Proteomics (2013) 12:825-31. doi:10.1074/mcp.O112.027094.
194. Borodovsky A, Ovaa H, Kolli N, Gan-Erdene T, Wilkinson KD, Ploegh HL, et al. Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family. Chem Biol (2002) 9:1149-59. doi:10.1016/S1074-5521(02)00248-X.
195. Hemelaar J, Galardy PJ, Borodovsky A, Kessler BM, Ploegh HL, Ovaa H. Chemistry-based functional proteomics: mechanism-based activity-profiling tools for ubiquitin and ubiquitin-like specific proteases. J Proteome Res (2004) 3:268-76. doi:10.1021/pr0341080.
196. Fonovic M, Bogyo M. Activity-based probes as a tool for functional proteomic analysis of proteases. Expert Rev Proteomics (2008) 5:721-30. doi:10.1586/14789450.5.5.721.
197. Love KR, Pandya RK, Spooner E, Ploegh HL. Ubiquitin C-terminal electrophiles are activity-based probes for identification and mechanistic study of ubiquitin conjugating machinery. ACS Chem Biol (2009) 4:275-87. doi:10.1021/cb9000348.
198. de Jong A, Merkx R, Berlin I, Rodenko B, Wijdeven RH, El Atmioui D, et al. Ubiquitin-based probes prepared by total synthesis to profile the activity of deubiquitinating enzymes. Chembiochem (2012) 13:2251-8. doi:10.1002/cbic.201200497.
199. Claessen JH, Witte MD, Yoder NC, Zhu AY, Spooner E, Ploegh HL. Catch-and-release probes applied to semi-intact cells reveal ubiquitin-specific protease expression in Chlamydia trachomatis infection. Chembiochem (2013) 14:343-52. doi:10.1002/cbic.201200701.
200. Persaud A, Alberts P, Amsen EM, Xiong X, Wasmuth J, Saadon Z, et al. Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays. Mol Syst Biol (2009) 5:333. doi:10.1038/msb.2009.85.
201. Persaud A, Rotin D. Use of proteome arrays to globally identify substrates for E3 ubiquitin ligases. Methods Mol Biol (2011) 759:215-24. doi:10.1007/978-1-61779-173-4_13.