Frontiers in Biology

, Volume 12, Issue 1, pp 19–48 | Cite as

Putting it all together: intrinsic and extrinsic mechanisms governing proteasome biogenesis




The 26S proteasome is at the heart of the ubiquitin-proteasome system, which is the key cellular pathway for the regulated degradation of proteins and enforcement of protein quality control. The 26S proteasome is an unusually large and complicated protease comprising a 28-subunit core particle (CP) capped by one or two 19-subunit regulatory particles (RP). Multiple activities within the RP process incoming ubiquitinated substrates for eventual degradation by the barrel-shaped CP. The large size and elaborate architecture of the proteasome have made it an exceptional model for understanding mechanistic themes in macromolecular assembly.


In the present work, we highlight the most recent mechanistic insights into proteasome assembly, with particular emphasis on intrinsic and extrinsic factors regulating proteasome biogenesis. We also describe new and exciting questions arising about how proteasome assembly is regulated and deregulated in normal and diseased cells.


A comprehensive literature search using the PubMed search engine was performed, and key findings yielding mechanistic insight into proteasome assembly were included in this review.


Key recent studies have revealed that proteasome biogenesis is dependent upon intrinsic features of the subunits themselves as well as extrinsic factors, many of which function as dedicated chaperones.


Cells rely on a diverse set of mechanistic strategies to ensure the rapid, efficient, and faithful assembly of proteasomes from their cognate subunits. Importantly, physiological as well as pathological changes to proteasome assembly are emerging as exciting paradigms to alter protein degradation in vivo.


proteasome assembly assembly chaperones ubiquitin-proteasome system proteolysis macromolecular complex 


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The authors apologize to their colleagues whose work could not be discussed due to space limitations. This work was supported in part by start-up funds from the Florida State University College of Medicine (R. J.T.Jr.) and by a Research Support Funds Grant from Indiana University- Purdue University Indianapolis (A.R.K.).


  1. Agarwal A K, Xing C, De Martino G N, Mizrachi D, Hernandez M D, Sousa A B, Martínez de Villarreal L, dos Santos H G, Garg A (2010). PSMB8 encoding the beta5i proteasome subunit is mutated in joint contractures, muscle atrophy, microcytic anemia, and panniculitisinduced lipodystrophy syndrome. Am J Hum Genet, 87(6): 866–872PubMedPubMedCentralCrossRefGoogle Scholar
  2. Akahane T, Sahara K, Yashiroda H, Tanaka K, Murata S (2013). Involvement of Bag6 and the TRC pathway in proteasome assembly. Nat Commun, 4: 2234PubMedCrossRefGoogle Scholar
  3. Arendt C S, Hochstrasser M (1997). Identification of the yeast 20S proteasome catalytic centers and subunit interactions required for active-site formation. Proc Natl Acad Sci USA, 94(14): 7156–7161PubMedPubMedCentralCrossRefGoogle Scholar
  4. Arendt C S, Hochstrasser M (1999). Eukaryotic 20S proteasome catalytic subunit propeptides prevent active site inactivation by Nterminal acetylation and promote particle assembly. EMBO J, 18(13): 3575–3585PubMedPubMedCentralCrossRefGoogle Scholar
  5. Arima K, Kinoshita A, Mishima H, Kanazawa N, Kaneko T, Mizushima T, Ichinose K, Nakamura H, Tsujino A, Kawakami A, Matsunaka M, Kasagi S, Kawano S, Kumagai S, Ohmura K, Mimori T, Hirano M, Ueno S, Tanaka K, Tanaka M, Toyoshima I, Sugino H, Yamakawa A, Tanaka K, Niikawa N, Furukawa F, Murata S, Eguchi K, Ida H, Yoshiura K (2011). Proteasome assembly defect due to a proteasome subunit beta type 8 (PSMB8) mutation causes the autoinflammatory disorder, Nakajo-Nishimura syndrome. Proc Natl Acad Sci USA, 108(36): 14914–14919PubMedPubMedCentralCrossRefGoogle Scholar
  6. Asano S, Fukuda Y, Beck F, Aufderheide A, Forster F, Danev R, Baumeister W (2015). Proteasomes. A molecular census of 26S proteasomes in intact neurons. Science, 347(6220): 439–442PubMedGoogle Scholar
  7. Aufderheide A, Beck F, Stengel F, Hartwig M, Schweitzer A, Pfeifer G, Goldberg A L, Sakata E, Baumeister W, Förster F (2015). Structural characterization of the interaction of Ubp6 with the 26S proteasome. Proc Natl Acad Sci USA, 112(28): 8626–8631PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bader M, Benjamin S, Wapinski O L, Smith D M, Goldberg A L, Steller H (2011). A conserved f box regulatory complex controls proteasome activity in Drosophila. Cell, 145(3): 371–382PubMedPubMedCentralCrossRefGoogle Scholar
  9. Bai M, Zhao X, Sahara K, Ohte Y, Hirano Y, Kaneko T, Yashiroda H, Murata S (2014). Assembly mechanisms of specialized core particles of the proteasome. Biomolecules, 4(3): 662–677PubMedPubMedCentralCrossRefGoogle Scholar
  10. Barrault M B, Richet N, Godard C, Murciano B, Le Tallec B, Rousseau E, Legrand P, Charbonnier J B, Le Du M H, Guerois R, Ochsenbein F, Peyroche A (2012). Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory particle subunits during the proteasome assembly. Proc Natl Acad Sci USA, 109(17): E1001–E1010 Google Scholar
  11. Barthelme D, Chen J Z, Grabenstatter J, Baker T A, Sauer R T (2014). Architecture and assembly of the archaeal Cdc48 20S proteasome. Proc Natl Acad Sci USA, 111(17): E1687–E1694 Google Scholar
  12. Barthelme D, Jauregui R, Sauer RT (2015). An ALS disease mutation in Cdc48/p97 impairs 20S proteasome binding and proteolytic communication. Protein Sci, 24:1521–1527PubMedPubMedCentralCrossRefGoogle Scholar
  13. Barthelme D, Sauer R T (2012a). Identification of the Cdc48 20S proteasome as an ancient AAA + proteolytic machine. Science, 337(6096): 843–846PubMedPubMedCentralCrossRefGoogle Scholar
  14. Barthelme D, Sauer RT (2012b). Identification of the Cdc48 20S proteasome as an ancient AAA + proteolytic machine. Science, 337(6096): 843–846PubMedPubMedCentralCrossRefGoogle Scholar
  15. Barthelme D, Sauer R T (2013). Bipartite determinants mediate an evolutionarily conserved interaction between Cdc48 and the 20S peptidase. Proc Natl Acad Sci USA, 110(9): 3327–3332PubMedPubMedCentralCrossRefGoogle Scholar
  16. Bashore C, Dambacher CM, Goodall E A, Matyskiela ME, Lander G C, Martin A (2015). Ubp6 deubiquitinase controls conformational dynamics and substrate degradation of the 26S proteasome. Nat Struct Mol Biol, 22(9): 712–719PubMedPubMedCentralCrossRefGoogle Scholar
  17. Basler M, Kirk C J, Groettrup M (2013). The immunoproteasome in antigen processing and other immunological functions. Curr Opin Immunol, 25(1): 74–80PubMedCrossRefGoogle Scholar
  18. Beck F, Unverdorben P, Bohn S, Schweitzer A, Pfeifer G, Sakata E, Nickell S, Plitzko J M, Villa E, Baumeister W, Forster F (2012). Near-atomic resolution structural model of the yeast 26S proteasome. Proc Natl Acad Sci USA, 109(37): 14870–14875PubMedPubMedCentralCrossRefGoogle Scholar
  19. Beckwith R, Estrin E, Worden E J, Martin A (2013). Reconstitution of the 26S proteasome reveals functional asymmetries in its AAA + unfoldase. Nat Struct Mol Biol, 20(10): 1164–1172PubMedPubMedCentralCrossRefGoogle Scholar
  20. Benaroudj N, Goldberg A L (2000). PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone. Nat Cell Biol, 2(11): 833–839PubMedCrossRefGoogle Scholar
  21. Braun B C, Glickman M, Kraft R, Dahlmann B, Kloetzel P M, Finley D, Schmidt M (1999). The base of the proteasome regulatory particle exhibits chaperone-like activity. Nat Cell Biol, 1(4): 221–226PubMedCrossRefGoogle Scholar
  22. Burri L, Hockendorff J, Boehm U, Klamp T, Dohmen R J, Levy F (2000). Identification and characterization of a mammalian protein interacting with 20S proteasome precursors. Proc Natl Acad Sci USA, 97(19): 10348–10353PubMedPubMedCentralCrossRefGoogle Scholar
  23. Cascio P (2014). PA28alphabeta: the enigmatic magic ring of the proteasome? Biomolecules, 4(2): 566–584PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chen P, Hochstrasser M (1996). Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly. Cell, 86(6): 961–972PubMedCrossRefGoogle Scholar
  25. Chu-Ping M, Slaughter C A, De Martino G N (1992). Purification and characterization of a protein inhibitor of the 20S proteasome (macropain). Biochim Biophys Acta, 1119(3): 303–311PubMedCrossRefGoogle Scholar
  26. Cohen-Kaplan V, Livneh I, Avni N, Fabre B, Ziv T, Kwon Y T, Ciechanover A (2016). p62- and ubiquitin-dependent stress-induced autophagy of the mammalian 26S proteasome. Proc Natl Acad Sci USA, 113(47): E7490–E7499PubMedCrossRefGoogle Scholar
  27. Colot H V, Park G, Turner G E, Ringelberg C, Crew C M, Litvinkova L, Weiss R L, Borkovich K A, Dunlap J C (2006). A high-throughput gene knockout procedure for Neurospora reveals functions for multiple transcription factors. Proc Natl Acad Sci USA, 103(27): 10352–10357PubMedPubMedCentralCrossRefGoogle Scholar
  28. da Fonseca P C, He J, Morris E P (2012). Molecular Model of the Human 26S Proteasome. Mol Cell, 46(1): 54–66PubMedCrossRefGoogle Scholar
  29. Dahlqvist J, Klar J, Tiwari N, Schuster J, Törmä H, Badhai J, Pujol R, van Steensel M A M, Brinkhuizen T, Gijezen L, Chaves A, Tadini G, Vahlquist A, Dahl N (2010). A single-nucleotide deletion in the POMP 5' UTR causes a transcriptional switch and altered epidermal proteasome distribution in KLICK genodermatosis. Am J Hum Genet, 86(4): 596–603PubMedPubMedCentralCrossRefGoogle Scholar
  30. Dambacher C M, Worden E J, Herzik M A, Martin A, Lander G C (2016). Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition. eLife, 5: e13027PubMedPubMedCentralCrossRefGoogle Scholar
  31. Dange T, Smith D, Noy T, Rommel P C, Jurzitza L, Cordero R J B, Legendre A, Finley D, Goldberg A L, Schmidt M (2011). Blm10 protein promotes proteasomal substrate turnover by an active gating mechanism. J Biol Chem, 286(50): 42830–42839PubMedPubMedCentralCrossRefGoogle Scholar
  32. De M, Jayarapu K, Elenich L, Monaco J J, Colbert R A, Griffin T A (2003). Beta 2 subunit propeptides influence cooperative proteasome assembly. J Biol Chem, 278(8): 6153–6159PubMedCrossRefGoogle Scholar
  33. De La Mota-Peynado A, Lee S Y, Pierce B M, Wani P, Singh C R, Roelofs J (2013). The proteasome-associated protein Ecm29 inhibits proteasomal ATPase activity and in vivo protein degradation by the proteasome. J Biol Chem, 288(41): 29467–29481CrossRefGoogle Scholar
  34. De Martino G N, Proske R J, Moomaw C R, Strong A A, Song X, Hisamatsu H, Tanaka K, Slaughter C A (1996). Identification, purification, and characterization of a PA700-dependent activator of the proteasome. J Biol Chem, 271(6): 3112–3118CrossRefGoogle Scholar
  35. Ding W X, Ni H M, Gao W, Yoshimori T, Stolz D B, Ron D, Yin X M (2007). Linking of autophagy to ubiquitin-proteasome system is important for the regulation of endoplasmic reticulum stress and cell viability. Am J Pathol, 171(2): 513–524PubMedPubMedCentralCrossRefGoogle Scholar
  36. Driscoll J, Brown M G, Finley D, Monaco J J (1993). MHC-linked LMP gene products specifically alter peptidase activities of the proteasome. Nature, 365(6443): 262–264PubMedCrossRefGoogle Scholar
  37. Enenkel C, Lehmann A, Kloetzel PM (1998). Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast. EMBO J, 17(21): 6144–6154PubMedPubMedCentralCrossRefGoogle Scholar
  38. Estrin E, Lopez-Blanco J R, Chacon P, Martin A (2013). Formation of an Intricate Helical Bundle Dictates the Assembly of the 26S Proteasome Lid. Structure, 21(9): 1624–1635PubMedCrossRefGoogle Scholar
  39. Fehlker M, Wendler P, Lehmann A, Enenkel C (2003). Blm3 is part of nascent proteasomes and is involved in a late stage of nuclear proteasome assembly. EMBO Rep, 4(10): 959–963PubMedPubMedCentralCrossRefGoogle Scholar
  40. Finley D (2009). Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem, 78(1): 477–513PubMedPubMedCentralCrossRefGoogle Scholar
  41. Forouzan D, Ammelburg M, Hobel C F, Stroh L J, Sessler N, Martin J, Lupas A N (2012). The archaeal proteasome is regulated by a network of AAA ATPases. J Biol Chem, 287(46): 39254–39262PubMedPubMedCentralCrossRefGoogle Scholar
  42. Forster A, Masters E I, Whitby F G, Robinson H, Hill C P (2005). The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions. Mol Cell, 18(5): 589–599PubMedCrossRefGoogle Scholar
  43. Fort P, Kajava A V, Delsuc F, Coux O (2015). Evolution of proteasome regulators in eukaryotes. Genome Biol Evol, 7(5): 1363–1379PubMedPubMedCentralCrossRefGoogle Scholar
  44. Frentzel S, Pesold-Hurt B, Seelig A, Kloetzel P M (1994). 20 S proteasomes are assembled via distinct precursor complexes. Processing of LMP2 and LMP7 proproteins takes place in 13–16 S preproteasome complexes. J Mol Biol, 236(4): 975–981PubMedGoogle Scholar
  45. Fricke B, Heink S, Steffen J, Kloetzel P M, Kruger E (2007). The proteasome maturation protein POMP facilitates major steps of 20S proteasome formation at the endoplasmic reticulum. EMBO Rep, 8(12): 1170–1175PubMedPubMedCentralCrossRefGoogle Scholar
  46. Fukunaga K, Kudo T, Toh-e A, Tanaka K, Saeki Y (2010). Dissection of the assembly pathway of the proteasome lid in Saccharomyces cerevisiae. Biochem Biophys Res Commun, 396(4): 1048–1053PubMedCrossRefGoogle Scholar
  47. Funakoshi M, Tomko R J, Kobayashi H, Hochstrasser M (2009). Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base. Cell, 137(5): 887–899PubMedPubMedCentralCrossRefGoogle Scholar
  48. Gaczynska M, Rock K L, Goldberg A L (1993). Gamma-interferon and expression of MHC genes regulate peptide hydrolysis by proteasomes. Nature, 365(6443): 264–267PubMedCrossRefGoogle Scholar
  49. Gerards W L, Enzlin J, Häner M, Hendriks ILA M, Aebi U, Bloemendal H, Boelens W (1997). The human alpha-type proteasomal subunit HsC8 forms a double ringlike structure, but does not assemble into proteasome-like particles with the beta-type subunits HsDelta or HsBPROS26. J Biol Chem, 272(15): 10080–10086PubMedCrossRefGoogle Scholar
  50. Gerards W L, de Jong W W, Bloemendal H, Boelens W (1998). The human proteasomal subunit HsC8 induces ring formation of other alpha-type subunits. J Mol Biol, 275(1): 113–121PubMedCrossRefGoogle Scholar
  51. Ghaemmaghami S, Huh W K, Bower K, Howson R W, Belle A, Dephoure N, O’Shea E K, Weissman J S (2003). Global analysis of protein expression in yeast. Nature, 425(6959): 737–741PubMedCrossRefGoogle Scholar
  52. Gille C, Goede A, Schlöetelburg C, Preißner R, Kloetzel P M, Göbel U B, Frömmel C (2003). A comprehensive view on proteasomal sequences: implications for the evolution of the proteasome. J Mol Biol, 326(5): 1437–1448PubMedCrossRefGoogle Scholar
  53. Gillette T G, Kumar B, Thompson D, Slaughter C A, De Martino G N (2008). Differential roles of the COOH termini of AAA subunits of PA700 (19 S regulator) in asymmetric assembly and activation of the 26 S proteasome. J Biol Chem, 283(46): 31813–31822PubMedPubMedCentralCrossRefGoogle Scholar
  54. Gomes A V (2013). Genetics of proteasome diseases. Scientifica (Cairo), 2013: 637629Google Scholar
  55. Gragnoli C, Cronsell J (2007). PSMD9 gene variants within NIDDM2 may rarely contribute to type 2 diabetes. J Cell Physiol, 212(3): 568–571PubMedCrossRefGoogle Scholar
  56. Griffin T A, Nandi D, Cruz M, Fehling H J, Kaer L V, Monaco J J, Colbert R A (1998). Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits. J Exp Med, 187(1): 97–104PubMedPubMedCentralCrossRefGoogle Scholar
  57. Griffin T A, Slack J P, McCluskey T S, Monaco J J, Colbert R A (2000). Identification of proteassemblin, a mammalian homologue of the yeast protein, Ump1p, that is required for normal proteasome assembly. Mol Cell Biol Res Commun, 3(4): 212–217PubMedCrossRefGoogle Scholar
  58. Groettrup M, Standera S, Stohwasser R, Kloetzel P M (1997). The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome. Proc Natl Acad Sci USA, 94(17): 8970–8975PubMedPubMedCentralCrossRefGoogle Scholar
  59. Groll M, Brandstetter H, Bartunik H, Bourenkow G, Huber R (2003). Investigations on the maturation and regulation of archaebacterial proteasomes. J Mol Biol, 327(1): 75–83PubMedCrossRefGoogle Scholar
  60. Groll M, Ditzel L, Löwe J, Stock D, Bochtler M, Bartunik H D, Huber R (1997). Structure of 20S proteasome from yeast at 2.4 A resolution. Nature, 386(6624): 463–471PubMedCrossRefGoogle Scholar
  61. Groll M, Glickman M H, Finley D, Bajorek M, Köhler A, Moroder L, Rubin D M, Huber R (2000). A gated channel into the proteasome core particle. Nat Struct Biol, 7(11): 1062–1067PubMedCrossRefGoogle Scholar
  62. Groll M, Heinemeyer W, Jager S, Ullrich T, Bochtler M, Wolf D H, Huber R (1999). The catalytic sites of 20S proteasomes and their role in subunit maturation: a mutational and crystallographic study. Proc Natl Acad Sci USA, 96(20): 10976–10983PubMedPubMedCentralCrossRefGoogle Scholar
  63. Haarer B, Aggeli D, Viggiano S, Burke D J, Amberg D C (2011). Novel interactions between actin and the proteasome revealed by complex haploinsufficiency. PLoS Genet, 7(9): e1002288PubMedPubMedCentralCrossRefGoogle Scholar
  64. Hanssum A, Zhong Z, Rousseau A, Krzyzosiak A, Sigurdardottir A, Bertolotti A (2014). An inducible chaperone adapts proteasome assembly to stress. Mol Cell, 55(4): 566–577PubMedPubMedCentralCrossRefGoogle Scholar
  65. Hatanaka A, Chen B, Sun J Q, Mano Y, Funakoshi M, Kobayashi H, Ju Y, Mizutani T, Shinmyozu K, Nakayama J, Miyamoto K, Uchida H, Oki M (2011). Fub1p, a novel protein isolated by boundary screening, binds the proteasome complex. Genes Genet Syst, 86(5): 305–314PubMedCrossRefGoogle Scholar
  66. Heinemeyer W, Fischer M, Krimmer T, Stachon U, Wolf D H (1997). The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J Biol Chem, 272(40): 25200–25209PubMedCrossRefGoogle Scholar
  67. Heink S, Ludwig D, Kloetzel P M, Kruger E (2005). IFN-gammainduced immune adaptation of the proteasome system is an accelerated and transient response. Proc Natl Acad Sci USA, 102(26): 9241–9246PubMedPubMedCentralCrossRefGoogle Scholar
  68. Hirano Y, Hayashi H, Iemura S, Hendil K B, Niwa S, Kishimoto T, Kasahara M, Natsume T, Tanaka K, Murata S (2006). Cooperation of multiple chaperones required for the assembly of mammalian 20S proteasomes. Mol Cell, 24(6): 977–984PubMedCrossRefGoogle Scholar
  69. Hirano Y, Hendil K B, Yashiroda H, Iemura S, Nagane R, Hioki Y, Natsume T, Tanaka K, Murata S (2005). A heterodimeric complex that promotes the assembly of mammalian 20S proteasomes. Nature, 437(7063): 1381–1385PubMedCrossRefGoogle Scholar
  70. Hirano Y, Kaneko T, Okamoto K, Bai M, Yashiroda H, Furuyama K, Kato K, Tanaka K, Murata S (2008). Dissecting beta-ring assembly pathway of the mammalian 20S proteasome. EMBO J, 27(16): 2204–2213PubMedPubMedCentralCrossRefGoogle Scholar
  71. Hoang B, Benavides A, Shi Y, Frost P, Lichtenstein A (2009). Effect of autophagy on multiple myeloma cell viability. Mol Cancer Ther, 8(7): 1974–1984PubMedCrossRefGoogle Scholar
  72. Hoefer M M, Boneberg E M, Grotegut S, Kusch J, Illges H (2006). Possible tetramerisation of the proteasome maturation factor POMP/ proteassemblin/hUmp1 and its subcellular localisation. Int J Biol Macromol, 38(3-5): 259–267PubMedCrossRefGoogle Scholar
  73. Huang X, Luan B, Wu J, Shi Y (2016). An atomic structure of the human 26S proteasome. Nat Struct Mol Biol, 23(9): 778–785PubMedCrossRefGoogle Scholar
  74. Huber E M, Heinemeyer W, Li X, Arendt C S, Hochstrasser M, Groll M (2016). A unified mechanism for proteolysis and autocatalytic activation in the 20S proteasome. Nat Commun, 7: 10900PubMedPubMedCentralCrossRefGoogle Scholar
  75. Huh WK, Falvo J V, Gerke L C, Carroll A S, Howson RW, Weissman J S, O’Shea E K (2003). Global analysis of protein localization in budding yeast. Nature, 425(6959): 686–691PubMedCrossRefGoogle Scholar
  76. Ishii K, Noda M, Yagi H, Thammaporn R, Seetaha S, Satoh T, Kato K, Uchiyama S (2015). Disassembly of the self-assembled, double-ring structure of proteasome alpha7 homo-tetradecamer by alpha6. Sci Rep, 5: 18167PubMedPubMedCentralCrossRefGoogle Scholar
  77. Isono E, Nishihara K, Saeki Y, Yashiroda H, Kamata N, Ge L, Ueda T, Kikuchi Y, Tanaka K, Nakano A, Toh-e A (2007). The assembly pathway of the 19S regulatory particle of the yeast 26S proteasome. Mol Biol Cell, 18(2): 569–580PubMedPubMedCentralCrossRefGoogle Scholar
  78. Iwata A, Riley B E, Johnston J A, Kopito R R (2005). HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem, 280(48): 40282–40292PubMedCrossRefGoogle Scholar
  79. Jager S, Groll M, Huber R, Wolf D H, Heinemeyer W (1999). Proteasome beta-type subunits: unequal roles of propeptides in core particle maturation and a hierarchy of active site function. J Mol Biol, 291(4): 997–1013PubMedCrossRefGoogle Scholar
  80. Ju D, Xie Y (2004). Proteasomal degradation of RPN4 via two distinct mechanisms, ubiquitin-dependent and-independent. J Biol Chem, 279(23): 23851–23854PubMedCrossRefGoogle Scholar
  81. Kaganovich D, Kopito R, Frydman J (2008). Misfolded proteins partition between two distinct quality control compartments. Nature, 454(7208): 1088–1095PubMedPubMedCentralCrossRefGoogle Scholar
  82. Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T, Tanaka K, Murata S (2009). Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones. Cell, 137(5): 914–925PubMedCrossRefGoogle Scholar
  83. Kim D U, Hayles J, Kim D, Wood V, Park H O, Won M, Yoo H S, Duhig T, Nam M, Palmer G, Han S, Jeffery L, Baek S T, Lee H, Shim Y S, Lee M, Kim L, Heo K S, Noh E J, Lee A R, Jang Y J, Chung K S, Choi S J, Park J Y, Park Y, Kim H M, Park S K, Park H J, Kang E J, Kim H B, Kang H S, Park H M, Kim K, Song K, Song K B, Nurse P, Hoe K L (2010a). Analysis of a genome-wide set of gene deletions in the fission yeast Schizosaccharomyces pombe. Nat Biotechnol, 28(6): 617–623PubMedPubMedCentralCrossRefGoogle Scholar
  84. Kim S, Saeki Y, Fukunaga K, Suzuki A, Takagi K, Yamane T, Tanaka K, Mizushima T, Kato K (2010b). Crystal structure of yeast rpn14, a chaperone of the 19 S regulatory particle of the proteasome. J Biol Chem, 285(20): 15159–15166PubMedPubMedCentralCrossRefGoogle Scholar
  85. Kim Y C, Snoberger A, Schupp J, Smith D M (2015). ATP binding to neighbouring subunits and intersubunit allosteric coupling underlie proteasomal ATPase function. Nat Commun, 6(8520):1Google Scholar
  86. Kingsbury D J, Griffin T A, Colbert R A (2000). Novel propeptide function in 20 S proteasome assembly influences beta subunit composition. J Biol Chem, 275(31): 24156–24162PubMedCrossRefGoogle Scholar
  87. Kleijnen M F, Roelofs J, Park S, Hathaway N A, Glickman M, King R W, Finley D (2007). Stability of the proteasome can be regulated allosterically through engagement of its proteolytic active sites. Nat Struct Mol Biol, 14(12): 1180–1188PubMedCrossRefGoogle Scholar
  88. Kloetzel P M (2004). Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII. Nat Immunol, 5(7): 661–669PubMedCrossRefGoogle Scholar
  89. Kock M, NunesMM, Hemann M, Kube S, Jürgen Dohmen R, Herzog F, Ramos P C, Wendler P (2015). Proteasome assembly from 15S precursors involves major conformational changes and recycling of the Pba1-Pba2 chaperone. Nat Commun, 6: 6123PubMedCrossRefGoogle Scholar
  90. Koizumi S, Irie T, Hirayama S, Sakurai Y, Yashiroda H, Naguro I, Ichijo H, Hamazaki J, Murata S (2016). The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction. eLife, 5: e18357PubMedPubMedCentralCrossRefGoogle Scholar
  91. Kragelund B B, Schenstrom S M, Rebula C A, Panse V G, Hartmann-Petersen R (2016). DSS1/Sem1, a multifunctional and intrinsically disordered protein. Trends Biochem Sci, 41(5): 446–459PubMedCrossRefGoogle Scholar
  92. Kriegenburg F, Seeger M, Saeki Y, Tanaka K, Lauridsen A M B, Hartmann-Petersen R, Hendil K B (2008). Mammalian 26S proteasomes remain intact during protein degradation. Cell, 135(2): 355–365PubMedCrossRefGoogle Scholar
  93. Kulak N A, Pichler G, Paron I, Nagaraj N, Mann M (2014). Minimal, encapsulated proteomic-sample processing applied to copy-number estimation in eukaryotic cells. Nat Methods, 11(3): 319–324PubMedCrossRefGoogle Scholar
  94. Kusmierczyk A R, Hochstrasser M (2008). Some assembly required: dedicated chaperones in eukaryotic proteasome biogenesis. Biol Chem, 389(9): 1143–1151PubMedPubMedCentralCrossRefGoogle Scholar
  95. Kusmierczyk A R, Kunjappu MJ, Funakoshi M, HochstrasserM(2008). A multimeric assembly factor controls the formation of alternative 20S proteasomes. Nat Struct Mol Biol, 15(3): 237–244PubMedCrossRefGoogle Scholar
  96. Kusmierczyk A R, Kunjappu M J, Kim R Y, Hochstrasser M (2011). A conserved 20S proteasome assembly factor requires a C-terminal HbYX motif for proteasomal precursor binding. Nat Struct Mol Biol, 18(5): 622–629PubMedPubMedCentralCrossRefGoogle Scholar
  97. Kwon Y D, Nagy I, Adams P D, Baumeister W, Jap B K (2004a). Crystal structures of the Rhodococcus proteasome with and without its propeptides: implications for the role of the pro-peptide in proteasome assembly. J Mol Biol, 335(1): 233–245PubMedCrossRefGoogle Scholar
  98. Kwon Y D, Nagy I, Adams P D, Baumeister W, Jap B K (2004b). Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly. J Mol Biol, 335(1): 233–245PubMedCrossRefGoogle Scholar
  99. Lander G C, Estrin E, Matyskiela M E, Bashore C, Nogales E, Martin A (2012). Complete subunit architecture of the proteasome regulatory particle. Nature, 482: 186–191PubMedPubMedCentralGoogle Scholar
  100. Lasker K, Forster F, Bohn S, Walzthoeni T, Villa E, Unverdorben P, Beck F, Aebersold R, Sali A, Baumeister W (2012). Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach. Proc Natl Acad Sci USA, 109(5): 1380–1387PubMedPubMedCentralCrossRefGoogle Scholar
  101. Le Tallec B, Barrault M B, Courbeyrette R, Guerois R, Marsolier-Kergoat M C, Peyroche A (2007). 20S proteasome assembly is orchestrated by two distinct pairs of chaperones in yeast and in mammals. Mol Cell, 27(4): 660–674PubMedCrossRefGoogle Scholar
  102. Le Tallec B, Barrault M B, Guerois R, Carre T, Peyroche A (2009). Hsm3/S5b participates in the assembly pathway of the 19S regulatory particle of the proteasome. Mol Cell, 33(3): 389–399PubMedCrossRefGoogle Scholar
  103. Lee S C, Shaw B D (2007). A novel interaction between Nmyristoylation and the 26S proteasome during cell morphogenesis. Mol Microbiol, 63(4): 1039–1053PubMedCrossRefGoogle Scholar
  104. Lee S Y, De la Mota-Peynado A, Roelofs J (2011). Loss of Rpt5 protein interactions with the core particle and Nas2 protein causes the formation of faulty proteasomes that are inhibited by Ecm29 protein. J Biol Chem, 286(42): 36641–36651PubMedPubMedCentralCrossRefGoogle Scholar
  105. Leggett D S, Hanna J, Borodovsky A, Crosas B, Schmidt M, Baker R T, Walz T, Ploegh H, Finley D (2002). Multiple associated proteins regulate proteasome structure and function. Mol Cell, 10(3): 495–507PubMedCrossRefGoogle Scholar
  106. Lehmann A, Janek K, Braun B, Kloetzel P M, Enenkel C (2002). 20 S proteasomes are imported as precursor complexes into the nucleus of yeast. J Mol Biol, 317(3): 401–413PubMedCrossRefGoogle Scholar
  107. Lehmann A, Niewienda A, Jechow K, Janek K, Enenkel C (2010). Ecm29 fulfils quality control functions in proteasome assembly. Mol Cell, 38(6): 879–888PubMedCrossRefGoogle Scholar
  108. Lehrbach N J, Ruvkun G (2016). Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic protease DDI-1. eLife, 5: e17721PubMedPubMedCentralCrossRefGoogle Scholar
  109. Lek M, Karczewski K J, Minikel E V, Samocha K E, Banks E, Fennell T, O’Donnell-Luria A H, Ware J S, Hill A J, Cummings B B, Tukiainen T, Birnbaum D P, Kosmicki J A, Duncan L E, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper D N, Deflaux N, De Pristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki M I, Moonshine A L, Natarajan P, Orozco L, Peloso G M, Poplin R, Rivas M A, Ruano-Rubio V, Rose S A, Ruderfer D M, Shakir K, Stenson P D, Stevens C, Thomas B P, Tiao G, Tusie-Luna M T, Weisburd B, Won H H, Yu D, Altshuler D M, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez J C, Gabriel S B, Getz G, Glatt S J, Hultman C M, Kathiresan S, Laakso M, McCarroll S, McCarthy M I, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf J M, Sklar P, Sullivan P F, Tuomilehto J, Tsuang M T, Watkins H C, Wilson J G, Daly M J, MacArthur D G (2016). Analysis of proteincoding genetic variation in 60,706 humans. Nature, 536(7616): 285–291PubMedPubMedCentralCrossRefGoogle Scholar
  110. Li D, Dong Q, Tao Q, Gu J, Cui Y, Jiang X, Yuan J, Li W, Xu R, Jin Y, Li P, Weaver D T, Ma Q, Liu X, Cao C (2015). c-Abl regulates proteasome abundance by controlling the ubiquitin-proteasomal degradation of PSMA7 subunit. Cell Reports, 10(4): 484–496PubMedCrossRefGoogle Scholar
  111. Li J, Zou C, Bai Y, Wazer D E, Band V, Gao Q (2006). DSS1 is required for the stability of BRCA2. Oncogene, 25(8): 1186–1194PubMedCrossRefGoogle Scholar
  112. Li X, Kusmierczyk A R, Wong P, Emili A, Hochstrasser M (2007). beta- Subunit appendages promote 20S proteasome assembly by overcoming an Ump1-dependent checkpoint. EMBO J, 26(9): 2339–2349PubMedPubMedCentralCrossRefGoogle Scholar
  113. Li X, Li Y, Arendt C S, Hochstrasser M (2016). Distinct elements in the proteasomal beta5 subunit propeptide required for autocatalytic processing and proteasome assembly. J Biol Chem, 291(4): 1991–2003PubMedCrossRefGoogle Scholar
  114. Li X, Thompson D, Kumar B, De Martino G N (2014). Molecular and cellular roles of PI31 (PSMF1) protein in regulation of proteasome function. J Biol Chem, 289(25): 17392–17405PubMedPubMedCentralCrossRefGoogle Scholar
  115. Liu J, Yuan X, Liu J, Tian L, Quan J, Liu J, Chen X, Wang Y, Shi Z, Zhang J (2012). Validation of the association between PSMA6 -8 C/ G polymorphism and type 2 diabetes mellitus in Chinese Dongxiang and Han populations. Diabetes Res Clin Pract, 98(2): 295–301PubMedCrossRefGoogle Scholar
  116. Lowe J, Stock D, Jap B, Zwickl P, Baumeister W, Huber R (1995). Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. Science, 268(5210): 533–539PubMedGoogle Scholar
  117. Luan B, Huang X, Wu J, Mei Z, Wang Y, Xue X, Yan C, Wang J, Finley D J, Shi Y, Wang F (2016). Structure of an endogenous yeast 26S proteasome reveals two major conformational states. Proc Natl Acad Sci USA, 113(10): 2642–2647PubMedPubMedCentralCrossRefGoogle Scholar
  118. Mannhaupt G, Schnall R, Karpov V, Vetter I, Feldmann H (1999). Rpn4p acts as a transcription factor by binding to PACE, a nonamer box found upstream of 26S proteasomal and other genes in yeast. FEBS Lett, 450(1-2): 27–34PubMedCrossRefGoogle Scholar
  119. Mao I, Liu J, Li X, Luo H (2008). REGgamma, a proteasome activator and beyond? Cellular and molecular life sciences. Cell Mol Life Sci, 65: 3971–3980PubMedCrossRefGoogle Scholar
  120. Marques A J, Glanemann C, Ramos P C, Dohmen R J (2007). The Cterminal extension of the beta7 subunit and activator complexes stabilize nascent 20 S proteasomes and promote their maturation. J Biol Chem, 282(48): 34869–34876PubMedCrossRefGoogle Scholar
  121. Marshall R S, Li F, Gemperline D C, Book A J, Vierstra R D (2015). Autophagic degradation of the 26S proteasome is mediated by the dual ATG8/ubiquitin receptor RPN10 in Arabidopsis. Mol Cell, 58(6): 1053–1066PubMedPubMedCentralCrossRefGoogle Scholar
  122. Marshall R S, McLoughlin F, Vierstra R D (2016). Autophagic turnover of inactive 26S Proteasomes in yeast is directed by the ubiquitin receptor Cue5 and the Hsp42 chaperone. Cell Reports, 16(6): 1717–1732PubMedCrossRefGoogle Scholar
  123. Matyskiela M E, Lander G C, Martin A (2013). Conformational switching of the 26S proteasome enables substrate degradation. Nat Struct Mol Biol, 20(7): 781–788PubMedPubMedCentralCrossRefGoogle Scholar
  124. Mayr J, Seemuller E, Muller S A, Engel A, Baumeister W (1998a). Late events in the assembly of 20S proteasomes. J Struct Biol, 124(2-3): 179–188PubMedCrossRefGoogle Scholar
  125. Mayr J, Seemuller E, Muller S A, Engel A, Baumeister W (1998b). Late events in the assembly of 20S proteasomes. J Struct Biol, 124(2-3): 179–188PubMedCrossRefGoogle Scholar
  126. Mayr J, Wang H R, Nederlof P, Baumeister W (1999). The import pathway of human and Thermoplasma 20S proteasomes into HeLa cell nuclei is different from that of classical NLS-bearing proteins. Biol Chem, 380(10): 1183–1192PubMedCrossRefGoogle Scholar
  127. Meiners S, Heyken D, Weller A, Ludwig A, Stangl K, Kloetzel P M, Kruger E (2003). Inhibition of proteasome activity induces concerted expression of proteasome genes and de novo formation of Mammalian proteasomes. J Biol Chem, 278(24): 21517–21525PubMedCrossRefGoogle Scholar
  128. Murata S, Sasaki K, Kishimoto T, Niwa S, Hayashi H, Takahama Y, Tanaka K (2007). Regulation of CD8+ T cell development by thymus-specific proteasomes. Science, 316(5829): 1349–1353PubMedCrossRefGoogle Scholar
  129. Nakamura Y, Umehara T, Tanaka A, Horikoshi M, Padmanabhan B, Yokoyama S (2007). Structural basis for the recognition between the regulatory particles Nas6 and Rpt3 of the yeast 26S proteasome. Biochem Biophys Res Commun, 359(3): 503–509PubMedCrossRefGoogle Scholar
  130. Nandi D, Woodward E, Ginsburg D B, Monaco J J (1997). Intermediates in the formation of mouse 20S proteasomes: implications for the assembly of precursor beta subunits. EMBO J, 16(17): 5363–5375PubMedPubMedCentralCrossRefGoogle Scholar
  131. Nederlof P M, Wang H R, Baumeister W (1995). Nuclear localization signals of human and Thermoplasma proteasomal alpha subunits are functional in vitro. Proc Natl Acad Sci USA, 92(26): 12060–12064PubMedPubMedCentralCrossRefGoogle Scholar
  132. Pack C G, Yukii H, Toh-e A, Kudo T, Tsuchiya H, Kaiho A, Sakata E, Murata S, Yokosawa H, Sako Y, Baumeister W, Tanaka K, Saeki Y (2014). Quantitative live-cell imaging reveals spatio-temporal dynamics and cytoplasmic assembly of the 26S proteasome. Nat Commun, 5: 3396PubMedCrossRefGoogle Scholar
  133. Padmanabhan A, Vuong S A, Hochstrasser M (2016). Assembly of an evolutionarily conserved alternative proteasome isoform in human cells. Cell Reports, 14(12): 2962–2974PubMedPubMedCentralCrossRefGoogle Scholar
  134. Pandey U B, Nie Z, Batlevi Y, McCray B A, Ritson G P, Nedelsky N B, Schwartz S L, DiProspero N A, Knight M A, Schuldiner O, Padmanabhan R, Hild M, Berry D L, Garza D, Hubbert C C, Yao T P, Baehrecke E H, Taylor J P (2007). HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature, 447(7146): 859–863PubMedCrossRefGoogle Scholar
  135. Panfair D, Ramamurthy A, Kusmierczyk A R (2015). Alpha-ring independent assembly of the 20S proteasome. Sci Rep, 5: 13130PubMedPubMedCentralCrossRefGoogle Scholar
  136. Paraskevopoulos K, Kriegenburg F, TathamMH, Rösner H I, Medina B, Larsen I B, Brandstrup R, Hardwick K G, Hay R T, Kragelund B B, Hartmann-Petersen R, Gordon C (2014). Dss1 is a 26S proteasome ubiquitin receptor. Mol Cell, 56(3): 453–461PubMedPubMedCentralCrossRefGoogle Scholar
  137. Park S, Kim W, Tian G, Gygi S P, Finley D (2011). Structural defects in the regulatory particle-core particle interface of the proteasome induce a novel proteasome stress response. J Biol Chem, 286(42): 36652–36666PubMedPubMedCentralCrossRefGoogle Scholar
  138. Park S, Li X, Kim HM, Singh C R, Tian G, HoytMA, Lovell S, Battaile K P, Zolkiewski M, Coffino P, Roelofs J, Cheng Y, Finley D (2013). Reconfiguration of the proteasome during chaperone-mediated assembly. Nature, 497(7450): 512–516PubMedPubMedCentralCrossRefGoogle Scholar
  139. Park S, Roelofs J, Kim W, Robert J, Schmidt M, Gygi S P, Finley D (2009). Hexameric assembly of the proteasomal ATPases is templated through their C termini. Nature, 459(7248): 866–870PubMedPubMedCentralCrossRefGoogle Scholar
  140. Pathare G R, Nagy I, Sledz P, Anderson D J, Zhou H J, Pardon E, Steyaert J, Forster F, Bracher A, Baumeister W (2014). Crystal structure of the proteasomal deubiquitylation module Rpn8-Rpn11. Proc Natl Acad Sci USA, 111(8): 2984–2989PubMedPubMedCentralCrossRefGoogle Scholar
  141. Peters L Z, Karmon O, David-Kadoch G, Hazan R, Yu T, Glickman M H, Ben-Aroya S (2015). The protein quality control machinery regulates its misassembled proteasome subunits. PLoS Genet, 11(4): e1005178PubMedPubMedCentralCrossRefGoogle Scholar
  142. Radhakrishnan S K, den Besten W, Deshaies R J (2014). p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition. eLife, 3: e01856PubMedPubMedCentralCrossRefGoogle Scholar
  143. Radhakrishnan S K, Lee C S, Young P, Beskow A, Chan J Y, Deshaies R J (2010). Transcription factor Nrf1 mediates the proteasome recovery pathway after proteasome inhibition in mammalian cells. Mol Cell, 38(1): 17–28PubMedPubMedCentralCrossRefGoogle Scholar
  144. Ramos P C, Hockendorff J, Johnson E S, Varshavsky A, Dohmen R J (1998). Ump1p is required for proper maturation of the 20S proteasome and becomes its substrate upon completion of the assembly. Cell, 92(4): 489–499PubMedCrossRefGoogle Scholar
  145. Ramos P C, Marques A J, London M K, Dohmen R J (2004). Role of Cterminal extensions of subunits beta2 and beta7 in assembly and activity of eukaryotic proteasomes. J Biol Chem, 279(14): 14323–14330PubMedCrossRefGoogle Scholar
  146. Reits E A, Benham A M, Plougastel B, Neefjes J, Trowsdale J (1997). Dynamics of proteasome distribution in living cells. EMBO J, 16(20): 6087–6094PubMedPubMedCentralCrossRefGoogle Scholar
  147. Roelofs J, Park S, Haas W, Tian G, McAllister F E, Huo Y, Lee B H, Zhang F, Shi Y, Gygi S P, Finley D (2009). Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature, 459(7248): 861–865PubMedPubMedCentralCrossRefGoogle Scholar
  148. Russell S J, Steger K A, Johnston S A (1999). Subcellular localization, stoichiometry, and protein levels of 26 S proteasome subunits in yeast. J Biol Chem, 274(31): 21943–21952PubMedCrossRefGoogle Scholar
  149. Sa-Moura B, Simões A M, Fraga J, Fernandes H, Abreu I A, Botelho H M, Gomes C M, Marques A J, Dohmen R J, Ramos P C, Macedo-Ribeiro S (2013). Biochemical and biophysical characterization of recombinant yeast proteasome maturation factor ump1. Comput Struct Biotechnol J, 7(8): e201304006PubMedPubMedCentralCrossRefGoogle Scholar
  150. Sadre-Bazzaz K, Whitby F G, Robinson H, Formosa T, Hill C P (2010). Structure of a Blm10 complex reveals common mechanisms for proteasome binding and gate opening. Mol Cell, 37(5): 728–735PubMedPubMedCentralCrossRefGoogle Scholar
  151. Saeki Y, Toh E A, Kudo T, Kawamura H, Tanaka K (2009). Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle. Cell, 137(5): 900–913PubMedCrossRefGoogle Scholar
  152. Sakata E, Stengel F, Fukunaga K, Zhou M, Saeki Y, Förster F, Baumeister W, Tanaka K, Robinson C V (2011). The catalytic activity of Ubp6 enhances maturation of the proteasomal regulatory particle. Mol Cell, 42(5): 637–649PubMedCrossRefGoogle Scholar
  153. Satoh T, Saeki Y, Hiromoto T, Wang Y H, Uekusa Y, Yagi H, Yoshihara H, Yagi-Utsumi M, Mizushima T, Tanaka K, Kato K (2014). Structural basis for proteasome formation controlled by an assembly chaperone nas2. Structure, 22(5): 731–743PubMedCrossRefGoogle Scholar
  154. Savulescu A F, Shorer H, Kleifeld O, Cohen I, Gruber R, GlickmanMH, Harel A (2011). Nuclear import of an intact preassembled proteasome particle. Mol Biol Cell, 22(6): 880–891PubMedPubMedCentralCrossRefGoogle Scholar
  155. Schmidt M, Haas W, Crosas B, Santamaria P G, Gygi S P, Walz T, Finley D (2005). The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle. Nat Struct Mol Biol, 12(4): 294–303PubMedCrossRefGoogle Scholar
  156. Schmidtke G, Kraft R, Kostka S, Henklein P, Frömmel C, Löwe J, Huber R, Kloetzel PM, Schmidt M(1996). Analysis of mammalian 20S proteasome biogenesis: the maturation of beta-subunits is an ordered two-step mechanism involving autocatalysis. EMBO J, 15: 6887–6898PubMedPubMedCentralGoogle Scholar
  157. Schmidtke G, Schmidt M, Kloetzel P M (1997). Maturation of mammalian 20 S proteasome: purification and characterization of 13 S and 16 S proteasome precursor complexes. J Mol Biol, 268(1): 95–106PubMedCrossRefGoogle Scholar
  158. Schweitzer A, Aufderheide A, Rudack T, Beck F, Pfeifer G, Plitzko JM, Sakata E, Schulten K, Förster F, Baumeister W (2016). Structure of the human 26S proteasome at a resolution of 3.9 A. Proc Natl Acad Sci USA, 113(28): 7816–7821PubMedPubMedCentralCrossRefGoogle Scholar
  159. Sha Z, Goldberg A L (2014). Proteasome-mediated processing of Nrf1 is essential for coordinate induction of all proteasome subunits and p97. Curr Biol, 24(14): 1573–1583PubMedPubMedCentralCrossRefGoogle Scholar
  160. Sharon M, Taverner T, Ambroggio X I, Deshaies R J, Robinson C V (2006). Structural organization of the 19S proteasome lid: insights from MS of intact complexes. PLoS Biol, 4(8): e267PubMedPubMedCentralCrossRefGoogle Scholar
  161. Sharon M, Witt S, Glasmacher E, Baumeister W, Robinson C V (2007). Mass spectrometry reveals the missing links in the assembly pathway of the bacterial 20 S proteasome. J Biol Chem, 282(25): 18448–18457PubMedCrossRefGoogle Scholar
  162. Shi Y, Chen X, Elsasser S, Stocks B B, Tian G, Lee B H, Shi Y, Zhang N, de Poot S A H, Tuebing F, Sun S, Vannoy J, Tarasov S G, Engen J R, Finley D, Walters K J (2016). Rpn1 provides adjacent receptor sites for substrate binding and deubiquitination by the proteasome. ScienceGoogle Scholar
  163. Shirozu R, Yashiroda H, Murata S (2015). Identification of minimum Rpn4-responsive elements in genes related to proteasome functions. FEBS Lett, 589(8): 933–940PubMedCrossRefGoogle Scholar
  164. Singh C R, Lovell S, Mehzabeen N, Chowdhury W Q, Geanes E S, Battaile K P, Roelofs J (2014). 1.15 A resolution structure of the proteasome-assembly chaperone Nas2 PDZ domain. Acta Crystallogr F Struct Biol Commun, 70(4): 418–423PubMedPubMedCentralCrossRefGoogle Scholar
  165. Sledz P, Unverdorben P, Beck F, Pfeifer G, Schweitzer A, Forster F, Baumeister W (2013). Structure of the 26S proteasome with ATPgammaS bound provides insights into the mechanism of nucleotidedependent substrate translocation. Proc Natl Acad Sci USA, 110(18): 7264–7269PubMedPubMedCentralCrossRefGoogle Scholar
  166. Smith D M, Chang S C, Park S, Finley D, Cheng Y, Goldberg A L (2007). Docking of the proteasomal ATPases’ carboxyl termini in the 20S proteasome’s alpha ring opens the gate for substrate entry. Mol Cell, 27(5): 731–744PubMedPubMedCentralCrossRefGoogle Scholar
  167. Sokolova V, Li F, Polovin G, Park S (2015). Proteasome activation is mediated via a functional switch of the Rpt6 C-terminal tail following chaperone-dependent assembly. Sci Rep, 5: 14909PubMedPubMedCentralCrossRefGoogle Scholar
  168. Stadtmueller B M, Hill C P (2011). Proteasome activators. Mol Cell, 41(1): 8–19PubMedPubMedCentralCrossRefGoogle Scholar
  169. Stadtmueller B M, Kish-Trier E, Ferrell K, Petersen C N, Robinson H, Myszka D G, Eckert D M, Formosa T, Hill C P (2012). Structure of a proteasome Pba1-Pba2 complex: implications for proteasome assembly, activation, and biological function. J Biol Chem, 287(44): 37371–37382PubMedPubMedCentralCrossRefGoogle Scholar
  170. Takagi K, Kim S, Yukii H, Ueno M, Morishita R, Endo Y, Kato K, Tanaka K, Saeki Y, Mizushima T (2012). Structural basis for specific recognition of Rpt1p, an ATPase subunit of 26S proteasome, by proteasome-dedicated chaperone Hsm3p. J Biol Chem, 287(15): 12172–12182PubMedPubMedCentralCrossRefGoogle Scholar
  171. Takagi K, Saeki Y, Yashiroda H, Yagi H, Kaiho A, Murata S, Yamane T, Tanaka K, Mizushima T, Kato K (2014). Pba3-Pba4 heterodimer acts as a molecular matchmaker in proteasome alpha-ring formation. Biochem Biophys Res Commun, 450(2): 1110–1114PubMedCrossRefGoogle Scholar
  172. Takeuchi J, Tamura T (2004). Recombinant ATPases of the yeast 26S proteasome activate protein degradation by the 20S proteasome. FEBS Lett, 565(1-3): 39–42PubMedCrossRefGoogle Scholar
  173. Tanaka K, Yoshimura T, Tamura T, Fujiwara T, Kumatori A, Ichihara A (1990). Possible mechanism of nuclear translocation of proteasomes. FEBS Lett, 271(1-2): 41–46PubMedCrossRefGoogle Scholar
  174. Thompson D, Hakala K, De Martino G N (2009). Subcomplexes of PA700, the 19S regulator of the 26 S proteasome, reveal relative roles of AAA subunits in 26 S proteasome assembly and activation and ATPase activity. J Biol Chem, 284(37): 24891–24903PubMedPubMedCentralCrossRefGoogle Scholar
  175. Tian G, Park S, Lee M J, Huck B, McAllister F, Hill C P, Gygi S P, Finley D (2011). An asymmetric interface between the regulatory and core particles of the proteasome. Nat Struct Mol Biol, 18(11): 1259–1267PubMedPubMedCentralCrossRefGoogle Scholar
  176. Tomko R J, Funakoshi M, Schneider K, Wang J, Hochstrasser M (2010). Heterohexameric ring arrangement of the eukaryotic proteasomal ATPases: implications for proteasome structure and assembly. Mol Cell, 38(3): 393–403PubMedPubMedCentralCrossRefGoogle Scholar
  177. Tomko R J Jr, Hochstrasser M (2011). Incorporation of the Rpn12 subunit couples completion of proteasome regulatory particle lid assembly to lid-base joining. Mol Cell, 44(6): 907–917PubMedPubMedCentralCrossRefGoogle Scholar
  178. Tomko R J, Hochstrasser M (2013). Molecular architecture and assembly of the eukaryotic proteasome. Annu Rev Biochem, 82(1): 415–445PubMedCrossRefGoogle Scholar
  179. Tomko R J, Hochstrasser M(2014). The intrinsically disordered Sem1 protein functions as a molecular tether during proteasome lid biogenesis. Mol Cell, 53(3): 433–443PubMedPubMedCentralCrossRefGoogle Scholar
  180. Tomko R J Jr, Taylor D W, Chen Z A, Wang H W, Rappsilber J, Hochstrasser M (2015). A Single alpha helix drives extensive remodeling of the proteasome lid and completion of regulatory particle assembly. Cell, 163(2): 432–444PubMedPubMedCentralCrossRefGoogle Scholar
  181. Uekusa Y, Okawa K, Yagi-Utsumi M, Serve O, Nakagawa Y, Mizushima T, Yagi H, Saeki Y, Tanaka K, Kato K (2014). Backbone (1)H, (1)(3)C and (1)(5)N assignments of yeast Ump1, an intrinsically disordered protein that functions as a proteasome assembly chaperone. Biomol NMR Assign, 8(2): 383–386PubMedCrossRefGoogle Scholar
  182. Unno M, Mizushima T, Morimoto Y, Tomisugi Y, Tanaka K, Yasuoka N, Tsukihara T (2002). The structure of the mammalian 20S proteasome at 2.75 A resolution. Structure, 10(5): 609–618PubMedCrossRefGoogle Scholar
  183. Unverdorben P, Beck F, led P, Schweitzer A, Pfeifer G, Plitzko J M, Baumeister W, Forster F (2014). Deep classification of a large cryo- EM dataset defines the conformational landscape of the 26S proteasome. Proc Natl Acad Sci USA, 111(15): 5544–5549PubMedPubMedCentralCrossRefGoogle Scholar
  184. Ustrell V, Hoffman L, Pratt G, Rechsteiner M (2002). PA200, a nuclear proteasome activator involved in DNA repair. EMBO J, 21(13): 3516–3525PubMedPubMedCentralCrossRefGoogle Scholar
  185. Velichutina I, Connerly P L, Arendt C S, Li X, Hochstrasser M (2004). Plasticity in eucaryotic 20S proteasome ring assembly revealed by a subunit deletion in yeast. EMBO J, 23(3): 500–510PubMedPubMedCentralCrossRefGoogle Scholar
  186. Verma R, et al (2002). Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science, 298(5593): 611–615PubMedCrossRefGoogle Scholar
  187. Volker C, Lupas A N (2002). Molecular evolution of proteasomes. Curr Top Microbiol Immunol, 268: 1–22PubMedGoogle Scholar
  188. Waite K A, De-La Mota-Peynado A, Vontz G, Roelofs J (2016). Starvation induces proteasome autophagy with different pathways for core and regulatory particles. J Biol Chem, 291(7): 3239–3253PubMedCrossRefGoogle Scholar
  189. Wang H R, Kania M, Baumeister W, Nederlof P M (1997). Import of human and Thermoplasma 20S proteasomes into nuclei of HeLa cells requires functional NLS sequences. Eur J Cell Biol, 73: 105–113PubMedGoogle Scholar
  190. Wang W, Chan J Y (2006). Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function. J Biol Chem, 281(28): 19676–19687PubMedGoogle Scholar
  191. Wani P S, Rowland M A, Ondracek A, Deeds E J, Roelofs J (2015). Maturation of the proteasome core particle induces an affinity switch that controls regulatory particle association. Nat Commun, 6: 6384PubMedPubMedCentralCrossRefGoogle Scholar
  192. Wani P S, Suppahia A, Capalla X, Ondracek A, Roelofs J (2016). Phosphorylation of the C-terminal tail of proteasome subunit alpha7 is required for binding of the proteasome quality control factor Ecm29. Sci Rep, 6: 27873PubMedPubMedCentralCrossRefGoogle Scholar
  193. Weberruss MH, Savulescu A F, Jando J, Bissinger T, Harel A, Glickman M H, Enenkel C (2013). Blm10 facilitates nuclear import of proteasome core particles. EMBO J, 32(20): 2697–2707PubMedPubMedCentralCrossRefGoogle Scholar
  194. Wei S J, Williams J G, Dang H, Darden T A, Betz B L, Humble M M, Chang F M, Trempus C S, Johnson K, Cannon R E, Tennant R W (2008). Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation. J Mol Biol, 383(3): 693–712PubMedCrossRefGoogle Scholar
  195. Welk V, Coux O, Kleene V, Abeza C, Trümbach D, Eickelberg O, Meiners S (2016). Inhibition of proteasome activity induces formation of alternative proteasome complexes. J Biol Chem, 291(25): 13147–13159PubMedCrossRefGoogle Scholar
  196. Wendler P, Lehmann A, Janek K, Baumgart S, Enenkel C (2004). The bipartite nuclear localization sequence of Rpn2 is required for nuclear import of proteasomal base complexes via karyopherin alphabeta and proteasome functions. J Biol Chem, 279(36): 37751–37762PubMedCrossRefGoogle Scholar
  197. Whitby F G, Masters E I, Kramer L, Knowlton J R, Yao Y, Wang C C, Hill C P (2000). Structural basis for the activation of 20S proteasomes by 11S regulators. Nature, 408(6808): 115–120PubMedCrossRefGoogle Scholar
  198. Witt E, Zantopf D, Schmidt M, Kraft R, Kloetzel P M, Kruger E (2000). Characterisation of the newly identified human Ump1 homologue POMP and analysis of LMP7(beta 5i) incorporation into 20 S proteasomes. J Mol Biol, 301(1): 1–9PubMedCrossRefGoogle Scholar
  199. Wollenberg K, Swaffield J C (2001). Evolution of proteasomal ATPases. Mol Biol Evol, 18(6): 962–974PubMedCrossRefGoogle Scholar
  200. Worden E J, Padovani C, Martin A (2014). Structure of the Rpn11-Rpn8 dimer reveals mechanisms of substrate deubiquitination during proteasomal degradation. Nat Struct Mol Biol, 21(3): 220–227PubMedCrossRefGoogle Scholar
  201. Xie Y, Varshavsky A (2001). RPN4 is a ligand, substrate, and transcriptional regulator of the 26S proteasome: a negative feedback circuit. Proc Natl Acad Sci USA, 98(6): 3056–3061PubMedPubMedCentralCrossRefGoogle Scholar
  202. Yao T, Cohen R E (2002). A cryptic protease couples deubiquitination and degradation by the proteasome. Nature, 419(6905): 403–407PubMedCrossRefGoogle Scholar
  203. Yao Y, Toth C R, Huang L, Wong M L, Dias P, Burlingame A L, Coffino P, Wang C C (1999). alpha5 subunit in Trypanosoma brucei proteasome can self-assemble to form a cylinder of four stacked heptamer rings. Biochem J, 344(Pt 2): 349–358PubMedPubMedCentralGoogle Scholar
  204. Yashiroda H, Mizushima T, Okamoto K, Kameyama T, Hayashi H, Kishimoto T, Niwa S, Kasahara M, Kurimoto E, Sakata E, Takagi K, Suzuki A, Hirano Y, Murata S, Kato K, Yamane T, Tanaka K (2008). Crystal structure of a chaperone complex that contributes to the assembly of yeast 20S proteasomes. Nat Struct Mol Biol, 15(3): 228–236PubMedCrossRefGoogle Scholar
  205. Yashiroda H, Toda Y, Otsu S, Takagi K, Mizushima T, Murata S (2015). N-terminal alpha7 deletion of the proteasome 20S core particle substitutes for yeast PI31 function. Mol Cell Biol, 35(1): 141–152PubMedCrossRefGoogle Scholar
  206. Yu Y, Smith D M, Kim H M, Rodriguez V, Goldberg A L, Cheng Y (2010). Interactions of PAN’s C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions. EMBO J, 29(3): 692–702PubMedCrossRefGoogle Scholar
  207. Yu Z, Livnat-Levanon N, Kleifeld O, Mansour W, Nakasone M A, Castaneda C A, Dixon E K, Fushman D, Reis N, Pick E, GlickmanM H (2015). Base-CP proteasome can serve as a platform for stepwise lid formation. Biosci Rep, 35(3): e00194PubMedPubMedCentralCrossRefGoogle Scholar
  208. Zaiss D M, Standera S, Kloetzel P M, Sijts A J (2002). PI31 is a modulator of proteasome formation and antigen processing. Proc Natl Acad Sci USA, 99(22): 14344–14349PubMedPubMedCentralCrossRefGoogle Scholar
  209. Zhang F, Hu M, Tian G, Zhang P, Finley D, Jeffrey P D, Shi Y (2009). Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol Cell, 34(4): 473–484PubMedPubMedCentralCrossRefGoogle Scholar
  210. Zhang Y, Lucocq J M, Yamamoto M, Hayes J D (2007). The NHB1 (Nterminal homology box 1) sequence in transcription factor Nrf1 is required to anchor it to the endoplasmic reticulum and also to enable its asparagine-glycosylation. Biochem J, 408(2): 161–172PubMedPubMedCentralCrossRefGoogle Scholar
  211. Zhu K, Dunner K Jr, McConkey D J (2010). Proteasome inhibitors activate autophagy as a cytoprotective response in human prostate cancer cells. Oncogene, 29(3): 451–462PubMedCrossRefGoogle Scholar
  212. Zuhl F, Seemuller E, Golbik R, Baumeister W (1997). Dissecting the assembly pathway of the 20S proteasome. FEBS Lett, 418(1-2): 189–194PubMedCrossRefGoogle Scholar
  213. Zwickl P, Kleinz J, Baumeister W (1994). Critical elements in proteasome assembly. Nat Struct Biol, 1(11): 765–770PubMedCrossRefGoogle Scholar
  214. Zwickl P, Ng D, Woo K M, Klenk H P, Goldberg A L (1999). An archaebacterial ATPase, homologous to ATPases in the eukaryotic 26S proteasome, activates protein breakdown by 20 S proteasomes. J Biol Chem, 274(37): 26008–26014PubMedCrossRefGoogle Scholar

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© Higher Education Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Biomedical SciencesFlorida State University College of MedicineTallahasseeUSA
  2. 2.Department of BiologyIndiana University-Purdue University IndianapolisIndianapolisUSA

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