1932

Abstract

The ubiquitin proteasome system controls the concentrations of regulatory proteins and removes damaged and misfolded proteins from cells. Proteins are targeted to the protease at the center of this system, the proteasome, by ubiquitin tags, but ubiquitin is also used as a signal in other cellular processes. Specificity is conferred by the size and structure of the ubiquitin tags, which are recognized by receptors associated with the different cellular processes. However, the ubiquitin code remains ambiguous, and the same ubiquitin tag can target different proteins to different fates. After binding substrate protein at the ubiquitin tag, the proteasome initiates degradation at a disordered region in the substrate. The proteasome has pronounced preferences for the initiation site, and its recognition represents a second component of the degradation signal.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biophys-070816-033719
2017-05-22
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/biophys/46/1/annurev-biophys-070816-033719.html?itemId=/content/journals/10.1146/annurev-biophys-070816-033719&mimeType=html&fmt=ahah

Literature Cited

  1. Alfano C, Faggiano S, Pastore A. 1.  2016. The ball and chain of polyubiquitin structures. Trends Biochem. Sci. 41:4371–85 [Google Scholar]
  2. Archer CT, Burdine L, Liu B, Ferdous A, Johnston SA, Kodadek T. 2.  2008. Physical and functional interactions of monoubiquitylated transactivators with the proteasome. J. Biol. Chem. 283:3121789–98 [Google Scholar]
  3. Asano S, Fukuda Y, Beck F, Aufderheide A, Förster F. 3.  et al. 2015. A molecular census of 26S proteasomes in intact neurons. Science 347:6220439–42 [Google Scholar]
  4. Aufderheide A, Beck F, Stengel F, Hartwig M, Schweitzer A. 4.  et al. 2015. Structural characterization of the interaction of Ubp6 with the 26S proteasome. PNAS 112:288626–31 [Google Scholar]
  5. Baker TA, Sauer RT. 5.  2012. ClpXP, an ATP-powered unfolding and protein-degradation machine. Biochim. Biophys. Acta 1823:115–28 [Google Scholar]
  6. Barthelme D, Sauer RT. 6.  2012. Identification of the Cdc48·20S proteasome as an ancient AAA+ proteolytic machine. Science 337:6096843–46 [Google Scholar]
  7. Bashore C, Dambacher CM, Goodall EA, Matyskiela ME, Lander GC, Martin A. 7.  2015. Ubp6 deubiquitinase controls conformational dynamics and substrate degradation of the 26S proteasome. Nat. Struct. Mol. Biol. 22:9712–19 [Google Scholar]
  8. Baumeister W, Walz J, Zühl F, Seemüller E. 8.  1998. The proteasome: paradigm of a self-compartmentalizing protease. Cell 92:3367–80 [Google Scholar]
  9. Beal R, Deveraux Q, Xia G, Rechsteiner M, Pickart C. 9.  1996. Surface hydrophobic residues of multi-ubiquitin chains essential for proteolytic targeting. PNAS 93:2861–66 [Google Scholar]
  10. Beckwith R, Estrin E, Worden EJ, Martin A. 10.  2013. Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA+ unfoldase. Nat. Struct. Mol. Biol. 20:101164–72 [Google Scholar]
  11. Berko D, Tabachnick-Cherny S, Shental-Bechor D, Cascio P, Mioletti S. 11.  et al. 2012. The direction of protein entry into the proteasome determines the variety of products and depends on the force needed to unfold its two termini. Mol. Cell 48:4601–11 [Google Scholar]
  12. Bertolaet BL, Clarke DJ, Wolff M, Watson MH, Henze M. 12.  et al. 2001. UBA domains of DNA damage-inducible proteins interact with ubiquitin. Nat. Struct. Biol. 8:5417–22 [Google Scholar]
  13. Besche HC, Sha Z, Kukushkin NV, Peth A. 13.  Hock E-M. et al. 2014. Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates. EMBO J 33:101159–76 [Google Scholar]
  14. Beskow A, Grimberg KB, Bott LC, Salomons FA, Dantuma NP, Young P. 14.  2009. A conserved unfoldase activity for the p97 AAA-ATPase in proteasomal degradation. J. Mol. Biol. 394:4732–46 [Google Scholar]
  15. Boname JM, Thomas M, Stagg HR, Xu P, Peng J, Lehner PJ. 15.  2010. Efficient internalization of MHC I requires lysine-11 and lysine-63 mixed linkage polyubiquitin chains. Traffic 11:2210–20 [Google Scholar]
  16. Borodovsky A, Kessler BM, Casagrande R, Overkleeft HS, Wilkinson KD, Ploegh HL. 16.  2001. A novel active site-directed probe specific for deubiquitylating enzymes reveals proteasome association of USP14. EMBO J 20:185187–96 [Google Scholar]
  17. Boutet SC, Disatnik M-H, Chan LS, Iori K, Rando TA. 17.  2007. Regulation of Pax3 by proteasomal degradation of monoubiquitinated protein in skeletal muscle progenitors. Cell 130:2349–62 [Google Scholar]
  18. Braten O, Livneh I, Ziv T, Admon A, Kehat I. 18.  et al. 2016. Numerous proteins with unique characteristics are degraded by the 26S proteasome following monoubiquitination. PNAS 113:32E4639–47 [Google Scholar]
  19. Bremm A, Moniz S, Mader J, Rocha S, Komander D. 19.  2014. Cezanne (OTUD7B) regulates HIF-1α homeostasis in a proteasome-independent manner. EMBO Rep 15:121268–77 [Google Scholar]
  20. Brown NG, VanderLinden R, Watson ER, Weissmann F, Ordureau A. 20.  et al. 2016. Dual RING E3 architectures regulate multiubiquitination and ubiquitin chain elongation by APC/C. Cell 165:61440–53 [Google Scholar]
  21. Budhidarmo R, Nakatani Y, Day CL. 21.  2012. RINGs hold the key to ubiquitin transfer. Trends Biochem. Sci. 37:258–65 [Google Scholar]
  22. Chen X, Barton LF, Chi Y, Clurman BE, Roberts JM. 22.  2007. Ubiquitin-independent degradation of cell-cycle inhibitors by the REGγ proteasome. Mol. Cell 26:6843–52 [Google Scholar]
  23. Chen X, Lee B-H, Finley D, Walters KJ. 23.  2010. Structure of proteasome ubiquitin receptor hRpn13 and its activation by the scaffolding protein hRpn2. Mol. Cell 38:3404–15 [Google Scholar]
  24. Chen ZJ, Sun LJ. 24.  2009. Nonproteolytic functions of ubiquitin in cell signaling. Mol. Cell 33:3275–86 [Google Scholar]
  25. Ciechanover A. 25.  2012. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Biochim. Biophys. Acta 1824:13–13 [Google Scholar]
  26. Craney A, Rape M. 26.  2013. Dynamic regulation of ubiquitin-dependent cell cycle control. Curr. Opin. Cell Biol. 25:6704–10 [Google Scholar]
  27. Crosas B, Hanna J, Kirkpatrick DS, Zhang DP, Tone Y. 27.  et al. 2006. Ubiquitin chains are remodeled at the proteasome by opposing ubiquitin ligase and deubiquitinating activities. Cell 127:71401–13 [Google Scholar]
  28. Csárdi G, Franks A, Choi DS, Airoldi EM, Drummond DA. 28.  2015. Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast. PLOS Genet 11:5e1005206 [Google Scholar]
  29. Dammer EB, Na CH, Xu P, Seyfried NT, Duong DM. 29.  et al. 2011. Polyubiquitin linkage profiles in three models of proteolytic stress suggest the etiology of Alzheimer disease. J. Biol. Chem. 286:1210457–65 [Google Scholar]
  30. DeMartino GN, Gillette TG. 30.  2007. Proteasomes: machines for all reasons. Cell 129:4659–62 [Google Scholar]
  31. Deshaies RJ, Joazeiro CAP. 31.  2009. RING domain E3 ubiquitin ligases. Annu. Rev. Biochem. 78:399–434 [Google Scholar]
  32. Deveraux Q, Ustrell V, Pickart C, Rechsteiner M. 32.  1994. A 26 S protease subunit that binds ubiquitin conjugates. J. Biol. Chem. 269:107059–61 [Google Scholar]
  33. Dimova NV, Hathaway NA, Lee B-H, Kirkpatrick DS, Berkowitz ML. 33.  et al. 2012. APC/C-mediated multiple monoubiquitylation provides an alternative degradation signal for cyclin B1. Nat. Cell Biol. 14:2168–76 [Google Scholar]
  34. Douglas PM, Dillin A. 34.  2010. Protein homeostasis and aging in neurodegeneration. J. Cell Biol. 190:5719–29 [Google Scholar]
  35. Dynek JN, Goncharov T, Dueber EC, Fedorova AV, Izrael-Tomasevic A. 35.  et al. 2010. C-IAP1 and UbcH5 promote K11-linked polyubiquitination of RIP1 in TNF signalling. EMBO J 29:244198–209 [Google Scholar]
  36. Elsasser S, Chandler-Militello D, Müller B, Hanna J, Finley D. 36.  2004. Rad23 and Rpn10 serve as alternative ubiquitin receptors for the proteasome. J. Biol. Chem. 279:2626817–22 [Google Scholar]
  37. Elsasser S, Finley D. 37.  2005. Delivery of ubiquitinated substrates to protein-unfolding machines. Nat. Cell Biol. 7:8742–49 [Google Scholar]
  38. Elsasser S, Gali RR, Schwickart M, Larsen CN, Leggett DS. 38.  et al. 2002. Proteasome subunit Rpn1 binds ubiquitin-like protein domains. Nat. Cell Biol. 4:9725–30 [Google Scholar]
  39. Erales J, Coffino P. 39.  2014. Ubiquitin-independent proteasomal degradation. Biochim. Biophys. Acta 1843:1216–21 [Google Scholar]
  40. Erpapazoglou Z, Walker O, Haguenauer-Tsapis R. 40.  2014. Versatile roles of K63-linked ubiquitin chains in trafficking. Cells 3:41027–88 [Google Scholar]
  41. Finley D. 41.  2009. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem. 78:477–513 [Google Scholar]
  42. Finley D. 42.  2011. Misfolded proteins driven to destruction by Hul5. Nat. Cell Biol. 13:111290–92 [Google Scholar]
  43. Finley D, Chen X, Walters KJ. 43.  2016. Gates, channels, and switches: elements of the proteasome machine. Trends Biochem. Sci. 41:177–93 [Google Scholar]
  44. Fishbain S, Inobe T, Israeli E, Chavali S, Yu H. 44.  et al. 2015. Sequence composition of disordered regions fine-tunes protein half-life. Nat. Struct. Mol. Biol. 22:3214–21 [Google Scholar]
  45. Fishbain S, Prakash S, Herrig A, Elsasser S, Matouschek A. 45.  2011. Rad23 escapes degradation because it lacks a proteasome initiation region. Nat. Commun. 2:192 [Google Scholar]
  46. Flick K, Ouni I, Wohlschlegel JA, Capati C, McDonald WH. 46.  2004. Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat. Cell Biol. 6:7634–41 [Google Scholar]
  47. Flynn JM, Neher SB, Kim Y-I, Sauer RT, Baker TA. 47.  2003. Proteomic discovery of cellular substrates of the ClpXP protease reveals five classes of ClpX-recognition signals. Mol. Cell 11:3671–83 [Google Scholar]
  48. Goebl MG, Goetsch L, Byers B. 48.  1994. The Ubc3 (Cdc34) ubiquitin-conjugating enzyme is ubiquitinated and phosphorylated in vivo. Mol. Cell. Biol. 14:53022–29 [Google Scholar]
  49. Grice GL, Lobb IT, Weekes MP, Gygi SP, Antrobus R, Nathan JA. 49.  2015. The proteasome distinguishes between heterotypic and homotypic lysine-11-linked polyubiquitin chains. Cell Rep 12:4545–53 [Google Scholar]
  50. Groll M, Bajorek M, Köhler A, Moroder L, Rubin DM. 50.  et al. 2000. A gated channel into the proteasome core particle. Nat. Struct. Biol. 7:111062–67 [Google Scholar]
  51. Guharoy M, Bhowmick P, Sallam M, Tompa P. 51.  2016. Tripartite degrons confer diversity and specificity on regulated protein degradation in the ubiquitin-proteasome system. Nat. Commun. 7:10239 [Google Scholar]
  52. Guo X, Wang X, Wang Z, Banerjee S, Yang J. 52.  et al. 2016. Site-specific proteasome phosphorylation controls cell proliferation and tumorigenesis. Nat. Cell Biol. 18:2202–12 [Google Scholar]
  53. Hamazaki J, Hirayama S, Murata S. 53.  2015. Redundant roles of Rpn10 and Rpn13 in recognition of ubiquitinated proteins and cellular homeostasis. PLOS Genet 11:7e1005401 [Google Scholar]
  54. Hamazaki J, Iemura S-I, Natsume T, Yashiroda H, Tanaka K, Murata S. 54.  2006. A novel proteasome interacting protein recruits the deubiquitinating enzyme UCH37 to 26S proteasomes. EMBO J 25:194524–36 [Google Scholar]
  55. Hanna J, Hathaway NA, Tone Y, Crosas B, Elsasser S. 55.  et al. 2006. Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation. Cell 127:199–111 [Google Scholar]
  56. Haupt Y, Maya R, Kazaz A, Oren M. 56.  1997. Mdm2 promotes the rapid degradation of p53. Nature 387:6630296–99 [Google Scholar]
  57. Heinen C, Acs K, Hoogstraten D, Dantuma NP. 57.  2011. C-terminal UBA domains protect ubiquitin receptors by preventing initiation of protein degradation. Nat. Commun. 2:191 [Google Scholar]
  58. Henderson A, Erales J, Hoyt MA, Coffino P. 58.  2011. Dependence of proteasome processing rate on substrate unfolding. J. Biol. Chem. 286:2017495–502 [Google Scholar]
  59. Hicke L, Dunn R. 59.  2003. Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu. Rev. Cell Dev. Biol. 19:141–72 [Google Scholar]
  60. Hjerpe R, Bett JS, Keuss MJ, Solovyova A, McWilliams TG. 60.  et al. 2016. UBQLN2 mediates autophagy-independent protein aggregate clearance by the proteasome. Cell 166:4935–49 [Google Scholar]
  61. Hochstrasser M, Varshavsky A. 61.  1990. In vivo degradation of a transcriptional regulator: the yeast α2 repressor. Cell 61:4697–708 [Google Scholar]
  62. Hock AK, Vousden KH. 62.  2014. The role of ubiquitin modification in the regulation of p53. Biochim. Biophys. Acta 1843:1137–49 [Google Scholar]
  63. Hofmann RM, Pickart CM. 63.  2001. In vitro assembly and recognition of Lys-63 polyubiquitin chains. J. Biol. Chem. 276:3027936–43 [Google Scholar]
  64. Holmberg CI, Staniszewski KE, Mensah KN, Matouschek A, Morimoto RI. 64.  2004. Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J 23:214307–18 [Google Scholar]
  65. Hoppe T, Matuschewski K, Rape M, Schlenker S, Ulrich HD, Jentsch S. 65.  2000. Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 102:5577–86 [Google Scholar]
  66. Hoyt MA, Zich J, Takeuchi J, Zhang M, Govaerts C, Coffino P. 66.  2006. Glycine–alanine repeats impair proper substrate unfolding by the proteasome. EMBO J 25:81720–29 [Google Scholar]
  67. Hurley JH, Stenmark H. 67.  2011. Molecular mechanisms of ubiquitin-dependent membrane traffic. Annu. Rev. Biophys. 40:119–42 [Google Scholar]
  68. Husnjak K, Dikic I. 68.  2012. Ubiquitin-binding proteins: decoders of ubiquitin-mediated cellular functions. Annu. Rev. Biochem. 81:291–322 [Google Scholar]
  69. Husnjak K, Elsasser S, Zhang N, Chen X, Randles L. 69.  et al. 2008. Proteasome subunit Rpn13 is a novel ubiquitin receptor. Nature 453:7194481–88 [Google Scholar]
  70. Inn K-S, Gack MU, Tokunaga F, Shi M, Wong L-Y. 70.  et al. 2011. Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction. Mol. Cell 41:3354–65 [Google Scholar]
  71. Inobe T, Fishbain S, Prakash S, Matouschek A. 71.  2011. Defining the geometry of the two-component proteasome degron. Nat. Chem. Biol. 7:3161–67 [Google Scholar]
  72. Inobe T, Matouschek A. 72.  2014. Paradigms of protein degradation by the proteasome. Curr. Opin. Struct. Biol. 24:156–64 [Google Scholar]
  73. Iosefson O, Olivares AO, Baker TA, Sauer RT. 73.  2015. Dissection of axial-pore loop function during unfolding and translocation by a AAA+ proteolytic machine. Cell Rep 12:61032–41 [Google Scholar]
  74. Isasa M, Katz EJ, Kim W, Yugo V, González S. 74.  et al. 2010. Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome. Mol. Cell 38:5733–45 [Google Scholar]
  75. Ivantsiv Y, Kaplun L, Tzirkin-Goldin R, Shabek N, Raveh D. 75.  2006. Unique role for the UbL-UbA protein Ddi1 in turnover of SCFUfo1 complexes. Mol. Cell. Biol. 26:51579–88 [Google Scholar]
  76. Iwai K, Fujita H, Sasaki Y. 76.  2014. Linear ubiquitin chains: NF-κB signalling, cell death and beyond. Nat. Rev. Mol. Cell. Biol. 15:8503–8 [Google Scholar]
  77. Jaakkola P, Mole DR, Tian Y-M, Wilson MI, Gielbert J. 77.  et al. 2001. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 292:5516468–72 [Google Scholar]
  78. Janse DM, Crosas B, Finley D, Church GM. 78.  2004. Localization to the proteasome is sufficient for degradation. J. Biol. Chem. 279:2021415–20 [Google Scholar]
  79. Jin L, Williamson A, Banerjee S, Philipp I, Rape M. 79.  2008. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133:4653–65 [Google Scholar]
  80. Johnson ES, Gonda DK, Varshavsky A. 80.  1990. Cis-trans recognition and subunit-specific degradation of short-lived proteins. Nature 346:6281287–91 [Google Scholar]
  81. Johnston JA, Johnson ES, Waller PR, Varshavsky A. 81.  1995. Methotrexate inhibits proteolysis of dihydrofolate reductase by the N-end rule pathway. J. Biol. Chem. 270:148172–78 [Google Scholar]
  82. Jonikas MC, Collins SR, Denic V, Oh E, Quan EM. 82.  et al. 2009. Comprehensive characterization of genes required for protein folding in the endoplasmic reticulum. Science 323:59221693–97 [Google Scholar]
  83. Ju D, Xie Y. 83.  2004. Proteasomal degradation of RPN4 via two distinct mechanisms, ubiquitin-dependent and -independent. J. Biol. Chem. 279:2323851–54 [Google Scholar]
  84. Ju D, Xie Y. 84.  2006. Identification of the preferential ubiquitination site and ubiquitin-dependent degradation signal of Rpn4. J. Biol. Chem. 281:1610657–62 [Google Scholar]
  85. Kaiser SE, Riley BE, Shaler TA, Trevino RS, Becker CH. 85.  et al. 2011. Protein standard absolute quantification (PSAQ) method for the measurement of cellular ubiquitin pools. Nat. Methods 8:8691–96 [Google Scholar]
  86. Kaplun L, Tzirkin R, Bakhrat A, Shabek N, Ivantsiv Y, Raveh D. 86.  2005. The DNA damage-inducible UbL-UbA protein Ddi1 participates in Mec1-mediated degradation of Ho endonuclease. Mol. Cell. Biol. 25:135355–62 [Google Scholar]
  87. Kee Y, Huibregtse JM. 87.  2007. Regulation of catalytic activities of HECT ubiquitin ligases. Biochem. Biophys. Res. Commun. 354:2329–33 [Google Scholar]
  88. Keiler KC, Waller PR, Sauer RT. 88.  1996. Role of a peptide tagging system in degradation of proteins synthesized from damaged messenger RNA. Science 271:5251990–93 [Google Scholar]
  89. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J. 89.  et al. 2011. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44:2325–40 [Google Scholar]
  90. Kirisako T, Kamei K, Murata S, Kato M, Fukumoto H. 90.  et al. 2006. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J 25:204877–87 [Google Scholar]
  91. Kirkpatrick DS, Hathaway NA, Hanna J, Elsasser S, Rush J. 91.  et al. 2006. Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology. Nat. Cell Biol. 8:7700–710 [Google Scholar]
  92. Kirstein J, Molière N, Dougan DA, Turgay K. 92.  2009. Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases. Nat. Rev. Microbiol. 7:8589–99 [Google Scholar]
  93. Komander D, Clague MJ, Urbé S. 93.  2009. Breaking the chains: structure and function of the deubiquitinases. Nat. Rev. Mol. Cell Biol. 10:8550–63 [Google Scholar]
  94. Komander D, Rape M. 94.  2012. The ubiquitin code. Annu. Rev. Biochem. 81:203–29 [Google Scholar]
  95. Krappmann D, Wulczyn FG, Scheidereit C. 95.  1996. Different mechanisms control signal-induced degradation and basal turnover of the NF-kappaB inhibitor IkappaB alpha in vivo. EMBO J 15:236716–26 [Google Scholar]
  96. Kraut DA, Matouschek A. 96.  2011. Proteasomal degradation from internal sites favors partial proteolysis via remote domain stabilization. ACS Chem. Biol. 6:101087–95 [Google Scholar]
  97. Kraut DA, Prakash S, Matouschek A. 97.  2007. To degrade or release: ubiquitin-chain remodeling. Trends Cell Biol 17:9419–21 [Google Scholar]
  98. Kravtsova-Ivantsiv Y, Ciechanover A. 98.  2012. Non-canonical ubiquitin-based signals for proteasomal degradation. J. Cell Sci. 125:3539–48 [Google Scholar]
  99. Kravtsova-Ivantsiv Y, Cohen S, Ciechanover A. 99.  2009. Modification by single ubiquitin moieties rather than polyubiquitination is sufficient for proteasomal processing of the p105 NF-κB precursor. Mol. Cell 33:4496–504 [Google Scholar]
  100. Kulathu Y, Komander D. 100.  2012. Atypical ubiquitylation—the unexplored world of polyubiquitin beyond Lys48 and Lys63 linkages. Nat. Rev. Mol. Cell Biol. 13:8508–23 [Google Scholar]
  101. Lam YA, Lawson TG, Velayutham M, Zweier JL, Pickart CM. 101.  2002. A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal. Nature 416:6882763–67 [Google Scholar]
  102. Lam YA, Xu W, DeMartino GN, Cohen RE. 102.  1997. Editing of ubiquitin conjugates by an isopeptidase in the 26S proteasome. Nature 385:6618737–40 [Google Scholar]
  103. Lander GC, Estrin E, Matyskiela ME, Bashore C, Nogales E, Martin A. 103.  2012. Complete subunit architecture of the proteasome regulatory particle. Nature 482:7384186–91 [Google Scholar]
  104. Lee B-H, Lee MJ, Park S, Oh D-C, Elsasser S. 104.  et al. 2010. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467:7312179–84 [Google Scholar]
  105. Lee B-H, Lu Y, Prado MA, Shi Y, Tian G. 105.  et al. 2016. USP14 deubiquitinates proteasome-bound substrates that are ubiquitinated at multiple sites. Nature 532:7599398–401 [Google Scholar]
  106. Lee C, Schwartz MP, Prakash S, Iwakura M, Matouschek A. 106.  2001. ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal. Mol. Cell 7:3627–37 [Google Scholar]
  107. Lee MJ, Lee B-H, Hanna J, King RW, Finley D. 107.  2011. Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol. Cell. Proteom. 10:5R110.003871 [Google Scholar]
  108. Leggett DS, Hanna J, Borodovsky A, Crosas B, Schmidt M. 108.  et al. 2002. Multiple associated proteins regulate proteasome structure and function. Mol. Cell 10:3495–507 [Google Scholar]
  109. Li X, Amazit L, Long W, Lonard DM, Monaco JJ, O'Malley BW. 109.  2007. Ubiquitin- and ATP-independent proteolytic turnover of p21 by the REGγ-proteasome pathway. Mol. Cell 26:6831–42 [Google Scholar]
  110. Liu C-W, Corboy MJ, DeMartino GN, Thomas PJ. 110.  2003. Endoproteolytic activity of the proteasome. Science 299:5605408–11 [Google Scholar]
  111. Liu Z, Gong Z, Jiang W-X, Yang J, Zhu W-K. 111.  et al. 2015. Lys63-linked ubiquitin chain adopts multiple conformational states for specific target recognition. eLife 4:548 [Google Scholar]
  112. Loriaux PM, Hoffmann A. 112.  2013. A protein turnover signaling motif controls the stimulus-sensitivity of stress response pathways. PLOS Comput. Biol. 9:2e1002932 [Google Scholar]
  113. Lu D, Girard JR, Li W, Mizrak A, Morgan DO. 113.  2015. Quantitative framework for ordered degradation of APC/C substrates. BMC Biol 13:196 [Google Scholar]
  114. Lu D, Hsiao JY, Davey NE, Van Voorhis VA, Foster SA. 114.  et al. 2014. Multiple mechanisms determine the order of APC/C substrate degradation in mitosis. J. Cell Biol. 207:123–39 [Google Scholar]
  115. Lu Y, Lee B-H, King RW, Finley D, Kirschner MW. 115.  2015. Substrate degradation by the proteasome: a single-molecule kinetic analysis. Science 348:62311250834 [Google Scholar]
  116. Lu Z, Hunter T. 116.  2010. Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell Cycle 9:122342–52 [Google Scholar]
  117. Luan B, Huang X, Wu J, Mei Z, Wang Y. 117.  et al. 2016. Structure of an endogenous yeast 26S proteasome reveals two major conformational states. PNAS 113:102642–47 [Google Scholar]
  118. Maldonado-Báez L, Wendland B. 118.  2006. Endocytic adaptors: recruiters, coordinators and regulators. Trends Cell Biol 16:10505–13 [Google Scholar]
  119. Martinez-Fonts K, Matouschek A. 119.  2016. A rapid and versatile method for generating proteins with defined ubiquitin chains. Biochemistry 55:121898–908 [Google Scholar]
  120. Matyskiela ME, Lander GC, Martin A. 120.  2013. Conformational switching of the 26S proteasome enables substrate degradation. Nat. Struct. Mol. Biol. 20:7781–88 [Google Scholar]
  121. Mayor T, Graumann J, Bryan J, MacCoss MJ, Deshaies RJ. 121.  2007. Quantitative profiling of ubiquitylated proteins reveals proteasome substrates and the substrate repertoire influenced by the Rpn10 receptor pathway. Mol. Cell. Proteom. 6:111885–95 [Google Scholar]
  122. Meyer H-J, Rape M. 122.  2014. Enhanced protein degradation by branched ubiquitin chains. Cell 157:4910–21 [Google Scholar]
  123. Murakami Y, Matsufuji S, Kameji T, Hayashi S, Igarashi K. 123.  et al. 1992. Ornithine decarboxylase is degraded by the 26S proteasome without ubiquitination. Nature 360:6404597–99 [Google Scholar]
  124. Nakamura M, Tokunaga F, Sakata S, Iwai K. 124.  2006. Mutual regulation of conventional protein kinase C and a ubiquitin ligase complex. Biochem. Biophys. Res. Commun. 351:2340–47 [Google Scholar]
  125. Nathan JA, Kim HT, Ting L, Gygi SP, Goldberg AL. 125.  2013. Why do cellular proteins linked to K63-polyubiquitin chains not associate with proteasomes?. EMBO J 32:4552–65 [Google Scholar]
  126. Nguyen LK, Dobrzyński M, Fey D, Kholodenko BN. 126.  2014. Polyubiquitin chain assembly and organization determine the dynamics of protein activation and degradation. Front. Physiol. 5:4 [Google Scholar]
  127. Nussbaum AK, Dick TP, Keilholz W, Schirle M, Stevanović S. 127.  et al. 1998. Cleavage motifs of the yeast 20S proteasome β subunits deduced from digests of enolase 1. PNAS 95:2112504–9 [Google Scholar]
  128. O'Dea EL, Barken D, Peralta RQ, Tran KT, Werner SL. 128.  et al. 2007. A homeostatic model of IκB metabolism to control constitutive NF‐κB activity. Mol. Syst. Biol. 3:1111 [Google Scholar]
  129. Peters J-M. 129.  2006. The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat. Rev. Mol. Cell Biol. 7:9644–56 [Google Scholar]
  130. Peth A, Besche HC, Goldberg AL. 130.  2009. Ubiquitinated proteins activate the proteasome by binding to Usp14/Ubp6, which causes 20S gate opening. Mol. Cell 36:5794–804 [Google Scholar]
  131. Pickart CM. 131.  2000. Ubiquitin in chains. Trends Biochem. Sci. 25:11544–48 [Google Scholar]
  132. Prakash S, Inobe T, Hatch AJ, Matouschek A. 132.  2009. Substrate selection by the proteasome during degradation of protein complexes. Nat. Chem. Biol. 5:129–36 [Google Scholar]
  133. Prakash S, Tian L, Ratliff KS, Lehotzky RE, Matouschek A. 133.  2004. An unstructured initiation site is required for efficient proteasome-mediated degradation. Nat. Struct. Mol. Biol. 11:9830–37 [Google Scholar]
  134. Pratt G, Rechsteiner M. 134.  2008. Proteasomes cleave at multiple sites within polyglutamine tracts: activation by PA28γ(K188E). J. Biol. Chem. 283:1912919–25 [Google Scholar]
  135. Qin Y, Zhou M-T, Hu M-M, Hu Y-H, Zhang J. 135.  et al. 2014. RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms. PLOS Pathog 10:9e1004358 [Google Scholar]
  136. Qiu X-B, Ouyang S-Y, Li C-J, Miao S, Wang L, Goldberg AL. 136.  2006. HRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37. EMBO J 25:245742–53 [Google Scholar]
  137. Raasi S, Orlov I, Fleming KG, Pickart CM. 137.  2004. Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains of HHR23A. J. Mol. Biol. 341:51367–79 [Google Scholar]
  138. Ramanathan HN, Ye Y. 138.  2012. Cellular strategies for making monoubiquitin signals. Crit. Rev. Biochem. Mol. Biol. 47:117–28 [Google Scholar]
  139. Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S. 139.  2001. Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48UFD1/NPL4, a ubiquitin-selective chaperone. Cell 107:5667–77 [Google Scholar]
  140. Rape M, Jentsch S. 140.  2002. Taking a bite: proteasomal protein processing. Nat. Cell Biol. 4:5E113–16 [Google Scholar]
  141. Rape M, Reddy SK, Kirschner MW. 141.  2006. The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 124:189–103 [Google Scholar]
  142. Ravid T, Hochstrasser M. 142.  2008. Diversity of degradation signals in the ubiquitin–proteasome system. Nat. Rev. Mol. Cell Biol. 9:9679–90 [Google Scholar]
  143. Rousseau E, Kojima R, Hoffner G, Djian P, Bertolotti A. 143.  2009. Misfolding of proteins with a polyglutamine expansion is facilitated by proteasomal chaperones. J. Biol. Chem. 284:31917–29 [Google Scholar]
  144. Saeki Y, Kudo T, Sone T, Kikuchi Y, Yokosawa H. 144.  et al. 2009. Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome. EMBO J 28:4359–71 [Google Scholar]
  145. Sauer RT, Baker TA. 145.  2011. AAA+ proteases: ATP-fueled machines of protein destruction. Annu. Rev. Biochem. 80:587–612 [Google Scholar]
  146. Schmidt M, Finley D. 146.  2014. Regulation of proteasome activity in health and disease. Biochim. Biophys. Acta 1843:113–25 [Google Scholar]
  147. Schrader EK, Harstad KG, Matouschek A. 147.  2009. Targeting proteins for degradation. Nat. Chem. Biol. 5:11815–22 [Google Scholar]
  148. Schwanhäusser B, Busse D, Li N, Dittmar G, Schuchhardt J. 148.  et al. 2011. Global quantification of mammalian gene expression control. Nature 473:7347337–42 [Google Scholar]
  149. Schwertman P, Bekker-Jensen S, Mailand N. 149.  2016. Regulation of DNA double-strand break repair by ubiquitin and ubiquitin-like modifiers. Nat. Rev. Mol. Cell Biol. 17:6379–94 [Google Scholar]
  150. Shabek N, Herman-Bachinsky Y, Buchsbaum S, Lewinson O, Haj-Yahya M. 150.  et al. 2012. The size of the proteasomal substrate determines whether its degradation will be mediated by mono- or polyubiquitylation. Mol. Cell 48:187–97 [Google Scholar]
  151. Sharipo A, Imreh M, Leonchiks A, Imreh S, Masucci MG. 151.  1998. A minimal glycine-alanine repeat prevents the interaction of ubiquitinated IκBα with the proteasome: a new mechanism for selective inhibition of proteolysis. Nat. Med. 4:8939–44 [Google Scholar]
  152. Shi Y, Chen X, Elsasser S, Stocks BB, Tian G. 152.  et al. 2016. Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. Science 351:6275aad9421 [Google Scholar]
  153. Shibatani T, Carlson EJ, Larabee F, McCormack AL, Früh K, Skach WR. 153.  2006. Global organization and function of mammalian cytosolic proteasome pools: implications for PA28 and 19S regulatory complexes. Mol. Biol. Cell 17:124962–71 [Google Scholar]
  154. Shimizu Y, Taraborrelli L, Walczak H. 154.  2015. Linear ubiquitination in immunity. Immunol. Rev. 266:1190–207 [Google Scholar]
  155. Silva GM, Finley D, Vogel C. 155.  2015. K63 polyubiquitination is a new modulator of the oxidative stress response. Nat. Struct. Mol. Biol. 22:2116–23 [Google Scholar]
  156. Sloper-Mould KE, Jemc JC, Pickart CM, Hicke L. 156.  2001. Distinct functional surface regions on ubiquitin. J. Biol. Chem. 276:3230483–89 [Google Scholar]
  157. Smit JJ, Sixma TK. 157.  2014. RBR E3-ligases at work. EMBO Rep 15:2142–54 [Google Scholar]
  158. Song EJ, Werner SL, Neubauer J, Stegmeier F, Aspden J. 158.  et al. 2010. The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome. Genes Dev 24:131434–47 [Google Scholar]
  159. Spence J, Gali RR, Dittmar G, Sherman F, Karin M, Finley D. 159.  2000. Cell cycle-regulated modification of the ribosome by a variant multiubiquitin chain. Cell 102:167–76 [Google Scholar]
  160. Stadtmueller BM, Hill CP. 160.  2011. Proteasome activators. Mol. Cell 41:18–19 [Google Scholar]
  161. Su V, Lau AF. 161.  2009. Ubiquitin-like and ubiquitin-associated domain proteins: significance in proteasomal degradation. Cell Mol. Life Sci. 66:172819–33 [Google Scholar]
  162. Śledź P, Förster F, Baumeister W. 162.  2013. Allosteric effects in the regulation of 26S proteasome activities. J. Mol. Biol. 425:91415–23 [Google Scholar]
  163. Śledź P, Unverdorben P, Beck F, Pfeifer G, Schweitzer A. 163.  et al. 2013. Structure of the 26S proteasome with ATP-γS bound provides insights into the mechanism of nucleotide-dependent substrate translocation. PNAS 110:187264–69 [Google Scholar]
  164. Takahashi K, Matouschek A, Inobe T. 164.  2015. Regulation of proteasomal degradation by modulating proteasomal initiation regions. ACS Chem. Biol. 10:112537–43 [Google Scholar]
  165. Takeuchi J, Chen H, Coffino P. 165.  2007. Proteasome substrate degradation requires association plus extended peptide. EMBO J 26:1123–31 [Google Scholar]
  166. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM. 166.  2000. Recognition of the polyubiquitin proteolytic signal. EMBO J 19:194–102 [Google Scholar]
  167. Tomko RJ Jr., Hochstrasser M. 167.  2013. Molecular architecture and assembly of the eukaryotic proteasome. Annu. Rev. Biochem. 82:415–45 [Google Scholar]
  168. Unverdorben P, Beck F, Śledź P, Schweitzer A, Pfeifer G. 168.  et al. 2014. Deep classification of a large cryo-EM dataset defines the conformational landscape of the 26S proteasome. PNAS 111:155544–49 [Google Scholar]
  169. van der Lee R, Lang B, Kruse K, Gsponer J, Sánchez de Groot N. 169.  et al. 2014. Intrinsically disordered segments affect protein half-life in the cell and during evolution. Cell Rep 8:61832–44 [Google Scholar]
  170. Varadan R, Assfalg M, Haririnia A, Raasi S, Pickart C, Fushman D. 170.  2004. Solution conformation of Lys63-linked di-ubiquitin chain provides clues to functional diversity of polyubiquitin signaling. J. Biol. Chem. 279:87055–63 [Google Scholar]
  171. Varadan R, Assfalg M, Raasi S, Pickart C, Fushman D. 171.  2005. Structural determinants for selective recognition of a Lys48-linked polyubiquitin chain by a UBA domain. Mol. Cell 18:6687–98 [Google Scholar]
  172. Varshavsky A. 172.  2011. The N-end rule pathway and regulation by proteolysis. Protein Sci 20:81298–345 [Google Scholar]
  173. Venkatraman P, Wetzel R, Tanaka M, Nukina N, Goldberg AL. 173.  2004. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 14:195–104 [Google Scholar]
  174. Verma R, Aravind L, Oania R, McDonald WH, Yates JR III. 174.  et al. 2002. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 298:5593611–15 [Google Scholar]
  175. Verma R, Chen S, Feldman R, Schieltz D, Yates J. 175.  et al. 2000. Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol. Biol. Cell 11:103425–39 [Google Scholar]
  176. Verma R, McDonald H, Yates JR III, Deshaies RJ. 176.  2001. Selective degradation of ubiquitinated Sic1 by purified 26S proteasome yields active S phase cyclin-Cdk. Mol. Cell 8:2439–48 [Google Scholar]
  177. Verma R, Oania R, Fang R, Smith GT, Deshaies RJ. 177.  2011. Cdc48/p97 mediates UV-dependent turnover of RNA Pol II. Mol. Cell 41:182–92 [Google Scholar]
  178. Verma R, Oania R, Graumann J, Deshaies RJ. 178.  2004. Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin-proteasome system. Cell 118:199–110 [Google Scholar]
  179. Wang Q, Young P, Walters KJ. 179.  2005. Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition. J. Mol. Biol. 348:3727–39 [Google Scholar]
  180. Weberruss MH, Savulescu AF, Jando J, Bissinger T, Harel A. 180.  et al. 2013. Blm10 facilitates nuclear import of proteasome core particles. EMBO J 32:202697–707 [Google Scholar]
  181. Whitby FG, Hill CP. 181.  2007. A versatile platform for inactivation and destruction. Structure 15:2137–38 [Google Scholar]
  182. Wickliffe KE, Lorenz S, Wemmer DE, Kuriyan J, Rape M. 182.  2011. The mechanism of linkage-specific ubiquitin chain elongation by a single-subunit E2. Cell 144:5769–81 [Google Scholar]
  183. Williamson A, Banerjee S, Zhu X, Philipp I, Iavarone AT, Rape M. 183.  2011. Regulation of ubiquitin chain initiation to control the timing of substrate degradation. Mol. Cell 42:6744–57 [Google Scholar]
  184. Williamson A, Wickliffe KE, Mellone BG, Song L, Karpen GH, Rape M. 184.  2009. Identification of a physiological E2 module for the human anaphase-promoting complex. PNAS 106:4318213–18 [Google Scholar]
  185. Wilmington SR, Matouschek A. 185.  2016. An inducible system for rapid degradation of specific cellular proteins using proteasome adaptors. PLOS ONE 11:4e0152679 [Google Scholar]
  186. Wojciechowski M, Szymczak P, Carrión-Vázquez M, Cieplak M. 186.  2014. Protein unfolding by biological unfoldases: insights from modeling. Biophys. J. 107:71661–68 [Google Scholar]
  187. Wu T, Merbl Y, Huo Y, Gallop JL, Tzur A, Kirschner MW. 187.  2010. UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex. PNAS 107:41355–60 [Google Scholar]
  188. Wu X, Karin M. 188.  2015. Emerging roles of Lys63-linked polyubiquitylation in immune responses. Immunol. Rev. 266:1161–74 [Google Scholar]
  189. Xie Y, Varshavsky A. 189.  2000. Physical association of ubiquitin ligases and the 26S proteasome. PNAS 97:62497–502 [Google Scholar]
  190. Xu P, Duong DM, Seyfried NT, Cheng D, Xie Y. 190.  et al. 2009. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137:1133–45 [Google Scholar]
  191. Yao T. 191.  2015. A timer to coordinate substrate processing by the 26S proteasome. Nat. Struct. Mol. Biol. 22:9652–53 [Google Scholar]
  192. Yao T, Cohen RE. 192.  2002. A cryptic protease couples deubiquitination and degradation by the proteasome. Nature 419:6905403–7 [Google Scholar]
  193. Yao T, Song L, Xu W, DeMartino GN, Florens L. 193.  et al. 2006. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat. Cell Biol. 8:9994–1002 [Google Scholar]
  194. Yau R, Rape M. 194.  2016. The increasing complexity of the ubiquitin code. Nat. Cell Biol. 18:6579–86 [Google Scholar]
  195. Ye Y, Rape M. 195.  2009. Building ubiquitin chains: E2 enzymes at work. Nat. Rev. Mol. Cell Biol. 10:11755–64 [Google Scholar]
  196. Yu H, Kago G, Yellman CM, Matouschek A. 196.  2016. Ubiquitin-like domains can target to the proteasome but proteolysis requires a disordered region. EMBO J 35:141522–36 [Google Scholar]
  197. Yu H, Singh Gautam AK, Wilmington SR, Wylie D, Martinez-Fonts K. 197.  et al. 2016. Conserved sequence preferences contribute to substrate recognition by the proteasome. J. Biol. Chem. 291:2814526–39 [Google Scholar]
  198. Zhang M, Pickart CM, Coffino P. 198.  2003. Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate. EMBO J 22:71488–96 [Google Scholar]
  199. Zhang N, Wang Q, Ehlinger A, Randles L, Lary JW. 199.  et al. 2009. Structure of the S5a-K48-linked diubiquitin complex and its interactions with Rpn13. Mol. Cell 35:3280–90 [Google Scholar]
  200. Zhang Z, Lv X, Yin W-C, Zhang X, Feng J. 200.  et al. 2013. Ter94 ATPase complex targets K11-linked ubiquitinated Ci to proteasomes for partial degradation. Dev. Cell 25:6636–44 [Google Scholar]
  201. Zhao M, Zhang N-Y, Zurawel A, Hansen KC, Liu C-W. 201.  2010. Degradation of some polyubiquitinated proteins requires an intrinsic proteasomal binding element in the substrates. J. Biol. Chem. 285:74771–80 [Google Scholar]
  202. Zhao S, Ulrich HD. 202.  2010. Distinct consequences of posttranslational modification by linear versus K63-linked polyubiquitin chains. PNAS 107:177704–9 [Google Scholar]
/content/journals/10.1146/annurev-biophys-070816-033719
Loading
/content/journals/10.1146/annurev-biophys-070816-033719
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error