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Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 1999 Sep 29;354(1389):1501–1511. doi: 10.1098/rstb.1999.0494

The proteasome: a macromolecular assembly designed for controlled proteolysis.

P Zwickl 1, D Voges 1, W Baumeister 1
PMCID: PMC1692663  PMID: 10582236

Abstract

In eukaryotic cells, the vast majority of proteins in the cytosol and nucleus are degraded via the proteasome-ubiquitin pathway. The 26S proteasome is a huge protein degradation machine of 2.5 MDa, built of approximately 35 different subunits. It contains a proteolytic core complex, the 20S proteasome and one or two 19S regulatory complexes which associate with the termini of the barrel-shaped 20S core. The 19S regulatory complex serves to recognize ubiquitylated target proteins and is implicated to have a role in their unfolding and translocation into the interior of the 20S complex where they are degraded into oligopeptides. While much progress has been made in recent years in elucidating the structure, assembly and enzymatic mechanism of the 20S complex, our knowledge of the functional organization of the 19S regulator is rather limited. Most of its subunits have been identified, but specific functions can be assigned to only a few of them.

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Selected References

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  1. Adams J., Behnke M., Chen S., Cruickshank A. A., Dick L. R., Grenier L., Klunder J. M., Ma Y. T., Plamondon L., Stein R. L. Potent and selective inhibitors of the proteasome: dipeptidyl boronic acids. Bioorg Med Chem Lett. 1998 Feb 17;8(4):333–338. doi: 10.1016/s0960-894x(98)00029-8. [DOI] [PubMed] [Google Scholar]
  2. Aravind L., Ponting C. P. Homologues of 26S proteasome subunits are regulators of transcription and translation. Protein Sci. 1998 May;7(5):1250–1254. doi: 10.1002/pro.5560070521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Asano K., Vornlocher H. P., Richter-Cook N. J., Merrick W. C., Hinnebusch A. G., Hershey J. W. Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly. J Biol Chem. 1997 Oct 24;272(43):27042–27052. doi: 10.1074/jbc.272.43.27042. [DOI] [PubMed] [Google Scholar]
  4. Babst M., Wendland B., Estepa E. J., Emr S. D. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function. EMBO J. 1998 Jun 1;17(11):2982–2993. doi: 10.1093/emboj/17.11.2982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baumeister W., Dahlmann B., Hegerl R., Kopp F., Kuehn L., Pfeifer G. Electron microscopy and image analysis of the multicatalytic proteinase. FEBS Lett. 1988 Dec 5;241(1-2):239–245. doi: 10.1016/0014-5793(88)81069-x. [DOI] [PubMed] [Google Scholar]
  6. Baumeister W., Walz J., Zühl F., Seemüller E. The proteasome: paradigm of a self-compartmentalizing protease. Cell. 1998 Feb 6;92(3):367–380. doi: 10.1016/s0092-8674(00)80929-0. [DOI] [PubMed] [Google Scholar]
  7. Beal R. E., Toscano-Cantaffa D., Young P., Rechsteiner M., Pickart C. M. The hydrophobic effect contributes to polyubiquitin chain recognition. Biochemistry. 1998 Mar 3;37(9):2925–2934. doi: 10.1021/bi972514p. [DOI] [PubMed] [Google Scholar]
  8. Beal R., Deveraux Q., Xia G., Rechsteiner M., Pickart C. Surface hydrophobic residues of multiubiquitin chains essential for proteolytic targeting. Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):861–866. doi: 10.1073/pnas.93.2.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Beuron F., Maurizi M. R., Belnap D. M., Kocsis E., Booy F. P., Kessel M., Steven A. C. At sixes and sevens: characterization of the symmetry mismatch of the ClpAP chaperone-assisted protease. J Struct Biol. 1998 Nov;123(3):248–259. doi: 10.1006/jsbi.1998.4039. [DOI] [PubMed] [Google Scholar]
  10. Beyer A. Sequence analysis of the AAA protein family. Protein Sci. 1997 Oct;6(10):2043–2058. doi: 10.1002/pro.5560061001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bochtler M., Ditzel L., Groll M., Huber R. Crystal structure of heat shock locus V (HslV) from Escherichia coli. Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6070–6074. doi: 10.1073/pnas.94.12.6070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bogyo M., McMaster J. S., Gaczynska M., Tortorella D., Goldberg A. L., Ploegh H. Covalent modification of the active site threonine of proteasomal beta subunits and the Escherichia coli homolog HslV by a new class of inhibitors. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6629–6634. doi: 10.1073/pnas.94.13.6629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Brannigan J. A., Dodson G., Duggleby H. J., Moody P. C., Smith J. L., Tomchick D. R., Murzin A. G. A protein catalytic framework with an N-terminal nucleophile is capable of self-activation. Nature. 1995 Nov 23;378(6555):416–419. doi: 10.1038/378416a0. [DOI] [PubMed] [Google Scholar]
  14. Brodsky J. L., McCracken A. A. ER-associated and proteasomemediated protein degradation: how two topologically restricted events came together. Trends Cell Biol. 1997 Apr;7(4):151–156. doi: 10.1016/S0962-8924(97)01020-9. [DOI] [PubMed] [Google Scholar]
  15. Chau V., Tobias J. W., Bachmair A., Marriott D., Ecker D. J., Gonda D. K., Varshavsky A. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989 Mar 24;243(4898):1576–1583. doi: 10.1126/science.2538923. [DOI] [PubMed] [Google Scholar]
  16. Chen P., Hochstrasser M. Autocatalytic subunit processing couples active site formation in the 20S proteasome to completion of assembly. Cell. 1996 Sep 20;86(6):961–972. doi: 10.1016/s0092-8674(00)80171-3. [DOI] [PubMed] [Google Scholar]
  17. Chu-Ping M., Slaughter C. A., DeMartino G. N. Purification and characterization of a protein inhibitor of the 20S proteasome (macropain). Biochim Biophys Acta. 1992 Mar 12;1119(3):303–311. doi: 10.1016/0167-4838(92)90218-3. [DOI] [PubMed] [Google Scholar]
  18. Chu-Ping M., Vu J. H., Proske R. J., Slaughter C. A., DeMartino G. N. Identification, purification, and characterization of a high molecular weight, ATP-dependent activator (PA700) of the 20 S proteasome. J Biol Chem. 1994 Feb 4;269(5):3539–3547. [PubMed] [Google Scholar]
  19. Cole S. T., Brosch R., Parkhill J., Garnier T., Churcher C., Harris D., Gordon S. V., Eiglmeier K., Gas S., Barry C. E., 3rd Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998 Jun 11;393(6685):537–544. doi: 10.1038/31159. [DOI] [PubMed] [Google Scholar]
  20. Coux O., Tanaka K., Goldberg A. L. Structure and functions of the 20S and 26S proteasomes. Annu Rev Biochem. 1996;65:801–847. doi: 10.1146/annurev.bi.65.070196.004101. [DOI] [PubMed] [Google Scholar]
  21. Dahlmann B., Kopp F., Kuehn L., Niedel B., Pfeifer G., Hegerl R., Baumeister W. The multicatalytic proteinase (prosome) is ubiquitous from eukaryotes to archaebacteria. FEBS Lett. 1989 Jul 17;251(1-2):125–131. doi: 10.1016/0014-5793(89)81441-3. [DOI] [PubMed] [Google Scholar]
  22. De Mot R., Nagy I., Walz J., Baumeister W. Proteasomes and other self-compartmentalizing proteases in prokaryotes. Trends Microbiol. 1999 Feb;7(2):88–92. doi: 10.1016/s0966-842x(98)01432-2. [DOI] [PubMed] [Google Scholar]
  23. Deveraux Q., Ustrell V., Pickart C., Rechsteiner M. A 26 S protease subunit that binds ubiquitin conjugates. J Biol Chem. 1994 Mar 11;269(10):7059–7061. [PubMed] [Google Scholar]
  24. Dick L. R., Cruikshank A. A., Destree A. T., Grenier L., McCormack T. A., Melandri F. D., Nunes S. L., Palombella V. J., Parent L. A., Plamondon L. Mechanistic studies on the inactivation of the proteasome by lactacystin in cultured cells. J Biol Chem. 1997 Jan 3;272(1):182–188. doi: 10.1074/jbc.272.1.182. [DOI] [PubMed] [Google Scholar]
  25. Dodson G., Wlodawer A. Catalytic triads and their relatives. Trends Biochem Sci. 1998 Sep;23(9):347–352. doi: 10.1016/s0968-0004(98)01254-7. [DOI] [PubMed] [Google Scholar]
  26. Dolenc I., Seemüller E., Baumeister W. Decelerated degradation of short peptides by the 20S proteasome. FEBS Lett. 1998 Sep 4;434(3):357–361. doi: 10.1016/s0014-5793(98)01010-2. [DOI] [PubMed] [Google Scholar]
  27. Dubiel W., Ferrell K., Pratt G., Rechsteiner M. Subunit 4 of the 26 S protease is a member of a novel eukaryotic ATPase family. J Biol Chem. 1992 Nov 15;267(32):22699–22702. [PubMed] [Google Scholar]
  28. Dubiel W., Ferrell K., Rechsteiner M. Subunits of the regulatory complex of the 26S protease. Mol Biol Rep. 1995;21(1):27–34. doi: 10.1007/BF00990967. [DOI] [PubMed] [Google Scholar]
  29. Dubiel W., Pratt G., Ferrell K., Rechsteiner M. Purification of an 11 S regulator of the multicatalytic protease. J Biol Chem. 1992 Nov 5;267(31):22369–22377. [PubMed] [Google Scholar]
  30. Enenkel C., Lehmann A., Kloetzel P. M. Subcellular distribution of proteasomes implicates a major location of protein degradation in the nuclear envelope-ER network in yeast. EMBO J. 1998 Nov 2;17(21):6144–6154. doi: 10.1093/emboj/17.21.6144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Etlinger J. D., Goldberg A. L. A soluble ATP-dependent proteolytic system responsible for the degradation of abnormal proteins in reticulocytes. Proc Natl Acad Sci U S A. 1977 Jan;74(1):54–58. doi: 10.1073/pnas.74.1.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Eytan E., Armon T., Heller H., Beck S., Hershko A. Ubiquitin C-terminal hydrolase activity associated with the 26 S protease complex. J Biol Chem. 1993 Mar 5;268(7):4668–4674. [PubMed] [Google Scholar]
  33. Fenteany G., Standaert R. F., Lane W. S., Choi S., Corey E. J., Schreiber S. L. Inhibition of proteasome activities and subunit-specific amino-terminal threonine modification by lactacystin. Science. 1995 May 5;268(5211):726–731. doi: 10.1126/science.7732382. [DOI] [PubMed] [Google Scholar]
  34. Finley D., Sadis S., Monia B. P., Boucher P., Ecker D. J., Crooke S. T., Chau V. Inhibition of proteolysis and cell cycle progression in a multiubiquitination-deficient yeast mutant. Mol Cell Biol. 1994 Aug;14(8):5501–5509. doi: 10.1128/mcb.14.8.5501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Finley D., Tanaka K., Mann C., Feldmann H., Hochstrasser M., Vierstra R., Johnston S., Hampton R., Haber J., Mccusker J. Unified nomenclature for subunits of the Saccharomyces cerevisiae proteasome regulatory particle. Trends Biochem Sci. 1998 Jul;23(7):244–245. doi: 10.1016/s0968-0004(98)01222-5. [DOI] [PubMed] [Google Scholar]
  36. Fu H., Sadis S., Rubin D. M., Glickman M., van Nocker S., Finley D., Vierstra R. D. Multiubiquitin chain binding and protein degradation are mediated by distinct domains within the 26 S proteasome subunit Mcb1. J Biol Chem. 1998 Jan 23;273(4):1970–1981. doi: 10.1074/jbc.273.4.1970. [DOI] [PubMed] [Google Scholar]
  37. Gerlinger U. M., Gückel R., Hoffmann M., Wolf D. H., Hilt W. Yeast cycloheximide-resistant crl mutants are proteasome mutants defective in protein degradation. Mol Biol Cell. 1997 Dec;8(12):2487–2499. doi: 10.1091/mbc.8.12.2487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Glickman M. H., Rubin D. M., Coux O., Wefes I., Pfeifer G., Cjeka Z., Baumeister W., Fried V. A., Finley D. A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3. Cell. 1998 Sep 4;94(5):615–623. doi: 10.1016/s0092-8674(00)81603-7. [DOI] [PubMed] [Google Scholar]
  39. Glickman M. H., Rubin D. M., Fried V. A., Finley D. The regulatory particle of the Saccharomyces cerevisiae proteasome. Mol Cell Biol. 1998 Jun;18(6):3149–3162. doi: 10.1128/mcb.18.6.3149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Goldberg A. L., Gaczynska M., Grant E., Michalek M., Rock K. L. Functions of the proteasome in antigen presentation. Cold Spring Harb Symp Quant Biol. 1995;60:479–490. doi: 10.1101/sqb.1995.060.01.052. [DOI] [PubMed] [Google Scholar]
  41. Gottesman S., Maurizi M. R., Wickner S. Regulatory subunits of energy-dependent proteases. Cell. 1997 Nov 14;91(4):435–438. doi: 10.1016/s0092-8674(00)80428-6. [DOI] [PubMed] [Google Scholar]
  42. Gottesman S. Proteases and their targets in Escherichia coli. Annu Rev Genet. 1996;30:465–506. doi: 10.1146/annurev.genet.30.1.465. [DOI] [PubMed] [Google Scholar]
  43. Gottesman S., Wickner S., Maurizi M. R. Protein quality control: triage by chaperones and proteases. Genes Dev. 1997 Apr 1;11(7):815–823. doi: 10.1101/gad.11.7.815. [DOI] [PubMed] [Google Scholar]
  44. Gray C. W., Slaughter C. A., DeMartino G. N. PA28 activator protein forms regulatory caps on proteasome stacked rings. J Mol Biol. 1994 Feb 11;236(1):7–15. doi: 10.1006/jmbi.1994.1113. [DOI] [PubMed] [Google Scholar]
  45. Groll M., Ditzel L., Löwe J., Stock D., Bochtler M., Bartunik H. D., Huber R. Structure of 20S proteasome from yeast at 2.4 A resolution. Nature. 1997 Apr 3;386(6624):463–471. doi: 10.1038/386463a0. [DOI] [PubMed] [Google Scholar]
  46. Grziwa A., Baumeister W., Dahlmann B., Kopp F. Localization of subunits in proteasomes from Thermoplasma acidophilum by immunoelectron microscopy. FEBS Lett. 1991 Sep 23;290(1-2):186–190. doi: 10.1016/0014-5793(91)81256-8. [DOI] [PubMed] [Google Scholar]
  47. Grziwa A., Maack S., Pühler G., Wiegand G., Baumeister W., Jaenicke R. Dissociation and reconstitution of the Thermoplasma proteasome. Eur J Biochem. 1994 Aug 1;223(3):1061–1067. doi: 10.1111/j.1432-1033.1994.tb19084.x. [DOI] [PubMed] [Google Scholar]
  48. Haas A., Reback P. M., Pratt G., Rechsteiner M. Ubiquitin-mediated degradation of histone H3 does not require the substrate-binding ubiquitin protein ligase, E3, or attachment of polyubiquitin chains. J Biol Chem. 1990 Dec 15;265(35):21664–21669. [PubMed] [Google Scholar]
  49. Haracska L., Udvardy A. Mapping the ubiquitin-binding domains in the p54 regulatory complex subunit of the Drosophila 26S protease. FEBS Lett. 1997 Jul 28;412(2):331–336. doi: 10.1016/s0014-5793(97)00808-9. [DOI] [PubMed] [Google Scholar]
  50. Heemels M. T., Ploegh H. Generation, translocation, and presentation of MHC class I-restricted peptides. Annu Rev Biochem. 1995;64:463–491. doi: 10.1146/annurev.bi.64.070195.002335. [DOI] [PubMed] [Google Scholar]
  51. Hegde A. N., Inokuchi K., Pei W., Casadio A., Ghirardi M., Chain D. G., Martin K. C., Kandel E. R., Schwartz J. H. Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia. Cell. 1997 Apr 4;89(1):115–126. doi: 10.1016/s0092-8674(00)80188-9. [DOI] [PubMed] [Google Scholar]
  52. Heinemeyer W., Fischer M., Krimmer T., Stachon U., Wolf D. H. The active sites of the eukaryotic 20 S proteasome and their involvement in subunit precursor processing. J Biol Chem. 1997 Oct 3;272(40):25200–25209. doi: 10.1074/jbc.272.40.25200. [DOI] [PubMed] [Google Scholar]
  53. Hershko A., Ciechanover A. The ubiquitin system. Annu Rev Biochem. 1998;67:425–479. doi: 10.1146/annurev.biochem.67.1.425. [DOI] [PubMed] [Google Scholar]
  54. Hershko A., Heller H. Occurrence of a polyubiquitin structure in ubiquitin-protein conjugates. Biochem Biophys Res Commun. 1985 May 16;128(3):1079–1086. doi: 10.1016/0006-291x(85)91050-2. [DOI] [PubMed] [Google Scholar]
  55. Hochstrasser M. Ubiquitin-dependent protein degradation. Annu Rev Genet. 1996;30:405–439. doi: 10.1146/annurev.genet.30.1.405. [DOI] [PubMed] [Google Scholar]
  56. Hoffman L., Pratt G., Rechsteiner M. Multiple forms of the 20 S multicatalytic and the 26 S ubiquitin/ATP-dependent proteases from rabbit reticulocyte lysate. J Biol Chem. 1992 Nov 5;267(31):22362–22368. [PubMed] [Google Scholar]
  57. Hofmann K., Bucher P. The PCI domain: a common theme in three multiprotein complexes. Trends Biochem Sci. 1998 Jun;23(6):204–205. doi: 10.1016/s0968-0004(98)01217-1. [DOI] [PubMed] [Google Scholar]
  58. Hough R., Pratt G., Rechsteiner M. Purification of two high molecular weight proteases from rabbit reticulocyte lysate. J Biol Chem. 1987 Jun 15;262(17):8303–8313. [PubMed] [Google Scholar]
  59. Hough R., Pratt G., Rechsteiner M. Ubiquitin-lysozyme conjugates. Identification and characterization of an ATP-dependent protease from rabbit reticulocyte lysates. J Biol Chem. 1986 Feb 15;261(5):2400–2408. [PubMed] [Google Scholar]
  60. Jentsch S. The ubiquitin-conjugation system. Annu Rev Genet. 1992;26:179–207. doi: 10.1146/annurev.ge.26.120192.001143. [DOI] [PubMed] [Google Scholar]
  61. Khan A. R., James M. N. Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes. Protein Sci. 1998 Apr;7(4):815–836. doi: 10.1002/pro.5560070401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Kisselev A. F., Akopian T. N., Goldberg A. L. Range of sizes of peptide products generated during degradation of different proteins by archaeal proteasomes. J Biol Chem. 1998 Jan 23;273(4):1982–1989. doi: 10.1074/jbc.273.4.1982. [DOI] [PubMed] [Google Scholar]
  63. Knipfer N., Shrader T. E. Inactivation of the 20S proteasome in Mycobacterium smegmatis. Mol Microbiol. 1997 Jul;25(2):375–383. doi: 10.1046/j.1365-2958.1997.4721837.x. [DOI] [PubMed] [Google Scholar]
  64. Knowlton J. R., Johnston S. C., Whitby F. G., Realini C., Zhang Z., Rechsteiner M., Hill C. P. Structure of the proteasome activator REGalpha (PA28alpha). Nature. 1997 Dec 11;390(6660):639–643. doi: 10.1038/37670. [DOI] [PubMed] [Google Scholar]
  65. Kobe B., Deisenhofer J. A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature. 1995 Mar 9;374(6518):183–186. doi: 10.1038/374183a0. [DOI] [PubMed] [Google Scholar]
  66. Koster A. J., Walz J., Lupas A., Baumeister W. Structural features of archaebacterial and eukaryotic proteasomes. Mol Biol Rep. 1995;21(1):11–20. doi: 10.1007/BF00990965. [DOI] [PubMed] [Google Scholar]
  67. Kuehn L., Dahlmann B. Reconstitution of proteasome activator PA28 from isolated subunits: optimal activity is associated with an alpha,beta-heteromultimer. FEBS Lett. 1996 Sep 30;394(2):183–186. doi: 10.1016/0014-5793(96)00946-5. [DOI] [PubMed] [Google Scholar]
  68. Larsen C. N., Finley D. Protein translocation channels in the proteasome and other proteases. Cell. 1997 Nov 14;91(4):431–434. doi: 10.1016/s0092-8674(00)80427-4. [DOI] [PubMed] [Google Scholar]
  69. Lee D. H., Goldberg A. L. Proteasome inhibitors: valuable new tools for cell biologists. Trends Cell Biol. 1998 Oct;8(10):397–403. doi: 10.1016/s0962-8924(98)01346-4. [DOI] [PubMed] [Google Scholar]
  70. Lenzen C. U., Steinmann D., Whiteheart S. W., Weis W. I. Crystal structure of the hexamerization domain of N-ethylmaleimide-sensitive fusion protein. Cell. 1998 Aug 21;94(4):525–536. doi: 10.1016/s0092-8674(00)81593-7. [DOI] [PubMed] [Google Scholar]
  71. Li X. C., Gu M. Z., Etlinger J. D. Isolation and characterization of a novel endogenous inhibitor of the proteasome. Biochemistry. 1991 Oct 8;30(40):9709–9715. doi: 10.1021/bi00104a020. [DOI] [PubMed] [Google Scholar]
  72. Lupas A., Baumeister W., Hofmann K. A repetitive sequence in subunits of the 26S proteasome and 20S cyclosome (anaphase-promoting complex). Trends Biochem Sci. 1997 Jun;22(6):195–196. doi: 10.1016/s0968-0004(97)01058-x. [DOI] [PubMed] [Google Scholar]
  73. Lupas A., Flanagan J. M., Tamura T., Baumeister W. Self-compartmentalizing proteases. Trends Biochem Sci. 1997 Oct;22(10):399–404. doi: 10.1016/s0968-0004(97)01117-1. [DOI] [PubMed] [Google Scholar]
  74. Lupas A., Koster A. J., Baumeister W. Structural features of 26S and 20S proteasomes. Enzyme Protein. 1993;47(4-6):252–273. doi: 10.1159/000468684. [DOI] [PubMed] [Google Scholar]
  75. Lupas A., Zwickl P., Baumeister W. Proteasome sequences in eubacteria. Trends Biochem Sci. 1994 Dec;19(12):533–534. doi: 10.1016/0968-0004(94)90054-x. [DOI] [PubMed] [Google Scholar]
  76. Löwe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 A resolution. Science. 1995 Apr 28;268(5210):533–539. doi: 10.1126/science.7725097. [DOI] [PubMed] [Google Scholar]
  77. Mayer T. U., Braun T., Jentsch S. Role of the proteasome in membrane extraction of a short-lived ER-transmembrane protein. EMBO J. 1998 Jun 15;17(12):3251–3257. doi: 10.1093/emboj/17.12.3251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Mayr J., Seemüller E., Müller S. A., Engel A., Baumeister W. Late events in the assembly of 20S proteasomes. J Struct Biol. 1998 Dec 15;124(2-3):179–188. doi: 10.1006/jsbi.1998.4068. [DOI] [PubMed] [Google Scholar]
  79. Missiakas D., Schwager F., Betton J. M., Georgopoulos C., Raina S. Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in overall proteolysis of misfolded proteins in Escherichia coli. EMBO J. 1996 Dec 16;15(24):6899–6909. [PMC free article] [PubMed] [Google Scholar]
  80. Monaco J. J., Nandi D. The genetics of proteasomes and antigen processing. Annu Rev Genet. 1995;29:729–754. doi: 10.1146/annurev.ge.29.120195.003501. [DOI] [PubMed] [Google Scholar]
  81. Murakami K., Etlinger J. D. Endogenous inhibitor of nonlysosomal high molecular weight protease and calcium-dependent protease. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7588–7592. doi: 10.1073/pnas.83.20.7588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Nagy I., Tamura T., Vanderleyden J., Baumeister W., De Mot R. The 20S proteasome of Streptomyces coelicolor. J Bacteriol. 1998 Oct;180(20):5448–5453. doi: 10.1128/jb.180.20.5448-5453.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Nandi D., Woodward E., Ginsburg D. B., Monaco J. J. Intermediates in the formation of mouse 20S proteasomes: implications for the assembly of precursor beta subunits. EMBO J. 1997 Sep 1;16(17):5363–5375. doi: 10.1093/emboj/16.17.5363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Omura S., Fujimoto T., Otoguro K., Matsuzaki K., Moriguchi R., Tanaka H., Sasaki Y. Lactacystin, a novel microbial metabolite, induces neuritogenesis of neuroblastoma cells. J Antibiot (Tokyo) 1991 Jan;44(1):113–116. doi: 10.7164/antibiotics.44.113. [DOI] [PubMed] [Google Scholar]
  85. Palmer A., Rivett A. J., Thomson S., Hendil K. B., Butcher G. W., Fuertes G., Knecht E. Subpopulations of proteasomes in rat liver nuclei, microsomes and cytosol. Biochem J. 1996 Jun 1;316(Pt 2):401–407. doi: 10.1042/bj3160401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Peters J. M., Cejka Z., Harris J. R., Kleinschmidt J. A., Baumeister W. Structural features of the 26 S proteasome complex. J Mol Biol. 1993 Dec 20;234(4):932–937. doi: 10.1006/jmbi.1993.1646. [DOI] [PubMed] [Google Scholar]
  87. Peters J. M., Franke W. W., Kleinschmidt J. A. Distinct 19 S and 20 S subcomplexes of the 26 S proteasome and their distribution in the nucleus and the cytoplasm. J Biol Chem. 1994 Mar 11;269(10):7709–7718. [PubMed] [Google Scholar]
  88. Pühler G., Weinkauf S., Bachmann L., Müller S., Engel A., Hegerl R., Baumeister W. Subunit stoichiometry and three-dimensional arrangement in proteasomes from Thermoplasma acidophilum. EMBO J. 1992 Apr;11(4):1607–1616. doi: 10.1002/j.1460-2075.1992.tb05206.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Ramos P. C., Höckendorff J., Johnson E. S., Varshavsky A., Dohmen R. J. Ump1p is required for proper maturation of the 20S proteasome and becomes its substrate upon completion of the assembly. Cell. 1998 Feb 20;92(4):489–499. doi: 10.1016/s0092-8674(00)80942-3. [DOI] [PubMed] [Google Scholar]
  90. Rechsteiner M., Hoffman L., Dubiel W. The multicatalytic and 26 S proteases. J Biol Chem. 1993 Mar 25;268(9):6065–6068. [PubMed] [Google Scholar]
  91. Reits E. A., Benham A. M., Plougastel B., Neefjes J., Trowsdale J. Dynamics of proteasome distribution in living cells. EMBO J. 1997 Oct 15;16(20):6087–6094. doi: 10.1093/emboj/16.20.6087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Rock K. L., Gramm C., Rothstein L., Clark K., Stein R., Dick L., Hwang D., Goldberg A. L. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell. 1994 Sep 9;78(5):761–771. doi: 10.1016/s0092-8674(94)90462-6. [DOI] [PubMed] [Google Scholar]
  93. Rohrwild M., Coux O., Huang H. C., Moerschell R. P., Yoo S. J., Seol J. H., Chung C. H., Goldberg A. L. HslV-HslU: A novel ATP-dependent protease complex in Escherichia coli related to the eukaryotic proteasome. Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5808–5813. doi: 10.1073/pnas.93.12.5808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Rohrwild M., Pfeifer G., Santarius U., Müller S. A., Huang H. C., Engel A., Baumeister W., Goldberg A. L. The ATP-dependent HslVU protease from Escherichia coli is a four-ring structure resembling the proteasome. Nat Struct Biol. 1997 Feb;4(2):133–139. doi: 10.1038/nsb0297-133. [DOI] [PubMed] [Google Scholar]
  95. Rubin D. M., Glickman M. H., Larsen C. N., Dhruvakumar S., Finley D. Active site mutants in the six regulatory particle ATPases reveal multiple roles for ATP in the proteasome. EMBO J. 1998 Sep 1;17(17):4909–4919. doi: 10.1093/emboj/17.17.4909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Rubin D. M., van Nocker S., Glickman M., Coux O., Wefes I., Sadis S., Fu H., Goldberg A., Vierstra R., Finley D. ATPase and ubiquitin-binding proteins of the yeast proteasome. Mol Biol Rep. 1997 Mar;24(1-2):17–26. doi: 10.1023/a:1006844305067. [DOI] [PubMed] [Google Scholar]
  97. Schauer T. M., Nesper M., Kehl M., Lottspeich F., Müller-Taubenberger A., Gerisch G., Baumeister W. Proteasomes from Dictyostelium discoideum: characterization of structure and function. J Struct Biol. 1993 Sep-Oct;111(2):135–147. doi: 10.1006/jsbi.1993.1044. [DOI] [PubMed] [Google Scholar]
  98. Schirmer E. C., Glover J. R., Singer M. A., Lindquist S. HSP100/Clp proteins: a common mechanism explains diverse functions. Trends Biochem Sci. 1996 Aug;21(8):289–296. [PubMed] [Google Scholar]
  99. Schmidtke G., Schmidt M., Kloetzel P. M. Maturation of mammalian 20 S proteasome: purification and characterization of 13 S and 16 S proteasome precursor complexes. J Mol Biol. 1997 Apr 25;268(1):95–106. doi: 10.1006/jmbi.1997.0947. [DOI] [PubMed] [Google Scholar]
  100. Seeger M., Kraft R., Ferrell K., Bech-Otschir D., Dumdey R., Schade R., Gordon C., Naumann M., Dubiel W. A novel protein complex involved in signal transduction possessing similarities to 26S proteasome subunits. FASEB J. 1998 Apr;12(6):469–478. [PubMed] [Google Scholar]
  101. Seemuller E., Lupas A., Baumeister W. Autocatalytic processing of the 20S proteasome. Nature. 1996 Aug 1;382(6590):468–471. doi: 10.1038/382468a0. [DOI] [PubMed] [Google Scholar]
  102. Seemüller E., Lupas A., Stock D., Löwe J., Huber R., Baumeister W. Proteasome from Thermoplasma acidophilum: a threonine protease. Science. 1995 Apr 28;268(5210):579–582. doi: 10.1126/science.7725107. [DOI] [PubMed] [Google Scholar]
  103. Sisodia S. S. Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial? Cell. 1998 Oct 2;95(1):1–4. doi: 10.1016/s0092-8674(00)81743-2. [DOI] [PubMed] [Google Scholar]
  104. Sommer T., Wolf D. H. Endoplasmic reticulum degradation: reverse protein flow of no return. FASEB J. 1997 Dec;11(14):1227–1233. doi: 10.1096/fasebj.11.14.9409541. [DOI] [PubMed] [Google Scholar]
  105. Tamura T., Nagy I., Lupas A., Lottspeich F., Cejka Z., Schoofs G., Tanaka K., De Mot R., Baumeister W. The first characterization of a eubacterial proteasome: the 20S complex of Rhodococcus. Curr Biol. 1995 Jul 1;5(7):766–774. doi: 10.1016/s0960-9822(95)00153-9. [DOI] [PubMed] [Google Scholar]
  106. Udvardy A. Purification and characterization of a multiprotein component of the Drosophila 26 S (1500 kDa) proteolytic complex. J Biol Chem. 1993 Apr 25;268(12):9055–9062. [PubMed] [Google Scholar]
  107. Varshavsky A. The N-end rule. Cell. 1992 May 29;69(5):725–735. doi: 10.1016/0092-8674(92)90285-k. [DOI] [PubMed] [Google Scholar]
  108. Varshavsky A. The ubiquitin system. Trends Biochem Sci. 1997 Oct;22(10):383–387. doi: 10.1016/s0968-0004(97)01122-5. [DOI] [PubMed] [Google Scholar]
  109. Voges D., Zwickl P., Baumeister W. The 26S proteasome: a molecular machine designed for controlled proteolysis. Annu Rev Biochem. 1999;68:1015–1068. doi: 10.1146/annurev.biochem.68.1.1015. [DOI] [PubMed] [Google Scholar]
  110. Walz J., Erdmann A., Kania M., Typke D., Koster A. J., Baumeister W. 26S proteasome structure revealed by three-dimensional electron microscopy. J Struct Biol. 1998 Jan;121(1):19–29. doi: 10.1006/jsbi.1998.3958. [DOI] [PubMed] [Google Scholar]
  111. Wang W., Chevray P. M., Nathans D. Mammalian Sug1 and c-Fos in the nuclear 26S proteasome. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8236–8240. doi: 10.1073/pnas.93.16.8236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Wei N., Tsuge T., Serino G., Dohmae N., Takio K., Matsui M., Deng X. W. The COP9 complex is conserved between plants and mammals and is related to the 26S proteasome regulatory complex. 1998 Jul 30-Aug 13Curr Biol. 8(16):919–922. doi: 10.1016/s0960-9822(07)00372-7. [DOI] [PubMed] [Google Scholar]
  113. Wenzel T., Baumeister W. Conformational constraints in protein degradation by the 20S proteasome. Nat Struct Biol. 1995 Mar;2(3):199–204. doi: 10.1038/nsb0395-199. [DOI] [PubMed] [Google Scholar]
  114. Wenzel T., Eckerskorn C., Lottspeich F., Baumeister W. Existence of a molecular ruler in proteasomes suggested by analysis of degradation products. FEBS Lett. 1994 Aug 1;349(2):205–209. doi: 10.1016/0014-5793(94)00665-2. [DOI] [PubMed] [Google Scholar]
  115. Wilkinson C. R., Wallace M., Morphew M., Perry P., Allshire R., Javerzat J. P., McIntosh J. R., Gordon C. Localization of the 26S proteasome during mitosis and meiosis in fission yeast. EMBO J. 1998 Nov 16;17(22):6465–6476. doi: 10.1093/emboj/17.22.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Wilkinson K. D., Urban M. K., Haas A. L. Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J Biol Chem. 1980 Aug 25;255(16):7529–7532. [PubMed] [Google Scholar]
  117. Wolf S., Nagy I., Lupas A., Pfeifer G., Cejka Z., Müller S. A., Engel A., De Mot R., Baumeister W. Characterization of ARC, a divergent member of the AAA ATPase family from Rhodococcus erythropolis. J Mol Biol. 1998 Mar 20;277(1):13–25. doi: 10.1006/jmbi.1997.1589. [DOI] [PubMed] [Google Scholar]
  118. Yoo S. J., Shim Y. K., Seong I. S., Seol J. H., Kang M. S., Chung C. H. Mutagenesis of two N-terminal Thr and five Ser residues in HslV, the proteolytic component of the ATP-dependent HslVU protease. FEBS Lett. 1997 Jul 21;412(1):57–60. doi: 10.1016/s0014-5793(97)00742-4. [DOI] [PubMed] [Google Scholar]
  119. Yoshimura T., Kameyama K., Takagi T., Ikai A., Tokunaga F., Koide T., Tanahashi N., Tamura T., Cejka Z., Baumeister W. Molecular characterization of the "26S" proteasome complex from rat liver. J Struct Biol. 1993 Nov-Dec;111(3):200–211. doi: 10.1006/jsbi.1993.1050. [DOI] [PubMed] [Google Scholar]
  120. Young P., Deveraux Q., Beal R. E., Pickart C. M., Rechsteiner M. Characterization of two polyubiquitin binding sites in the 26 S protease subunit 5a. J Biol Chem. 1998 Mar 6;273(10):5461–5467. doi: 10.1074/jbc.273.10.5461. [DOI] [PubMed] [Google Scholar]
  121. Yu R. C., Hanson P. I., Jahn R., Brünger A. T. Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP. Nat Struct Biol. 1998 Sep;5(9):803–811. doi: 10.1038/1843. [DOI] [PubMed] [Google Scholar]
  122. Zwickl P., Grziwa A., Pühler G., Dahlmann B., Lottspeich F., Baumeister W. Primary structure of the Thermoplasma proteasome and its implications for the structure, function, and evolution of the multicatalytic proteinase. Biochemistry. 1992 Feb 4;31(4):964–972. doi: 10.1021/bi00119a004. [DOI] [PubMed] [Google Scholar]
  123. Zwickl P., Kleinz J., Baumeister W. Critical elements in proteasome assembly. Nat Struct Biol. 1994 Nov;1(11):765–770. doi: 10.1038/nsb1194-765. [DOI] [PubMed] [Google Scholar]
  124. Zwickl P., Lottspeich F., Baumeister W. Expression of functional Thermoplasma acidophilum proteasomes in Escherichia coli. FEBS Lett. 1992 Nov 9;312(2-3):157–160. doi: 10.1016/0014-5793(92)80925-7. [DOI] [PubMed] [Google Scholar]
  125. Zühl F., Seemüller E., Golbik R., Baumeister W. Dissecting the assembly pathway of the 20S proteasome. FEBS Lett. 1997 Nov 24;418(1-2):189–194. doi: 10.1016/s0014-5793(97)01370-7. [DOI] [PubMed] [Google Scholar]
  126. Zühl F., Tamura T., Dolenc I., Cejka Z., Nagy I., De Mot R., Baumeister W. Subunit topology of the Rhodococcus proteasome. FEBS Lett. 1997 Jan 2;400(1):83–90. doi: 10.1016/s0014-5793(96)01403-2. [DOI] [PubMed] [Google Scholar]
  127. van Nocker S., Sadis S., Rubin D. M., Glickman M., Fu H., Coux O., Wefes I., Finley D., Vierstra R. D. The multiubiquitin-chain-binding protein Mcb1 is a component of the 26S proteasome in Saccharomyces cerevisiae and plays a nonessential, substrate-specific role in protein turnover. Mol Cell Biol. 1996 Nov;16(11):6020–6028. doi: 10.1128/mcb.16.11.6020. [DOI] [PMC free article] [PubMed] [Google Scholar]

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