Abstract
The accumulation of misfolded protein into insoluble inclusions is a pathological hallmark of many diseases. How these inclusions form and their role in the degenerative process is still unknown. Recently, a cellular response to the accumulation of misfolded protein was described, and the resulting structures were termed Aggresomes. Aggresomes occur in cells due to impairment of intracellular degradation pathways, and are insoluble inclusions associated with a rearranged intermediate filament network. Aggresomes form by the microtubule and dynein-dynactin-dependent delivery of small microaggregates of protein to a central cellular location, in most cases the centrosome. In this chapter, the characteristics of aggresomes are described, followed by a discussion of the relationship of aggresomes to the general class of ubiquitin-intermediate filament diseases (most notably characterized by Lewy Bodies in Parkinson’s Disease, intranuclear inclusions in Huntington’s Disease, and Bunina Bodies in amyotrophic lateral sclerosis), and conclude with potential mechanisms for aggresome formation. Aggresomes have the potential to provide a mechanistic clue to the pathogenesis of ubiquitin-intermediate filament disorders.
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References
Aguilera, M., Oliveros, M., Martinez-Padron, M., Barbas, J.A., and Ferrus, A. (2000). Ariadne-1: a vital Drosophila gene is required in development and defines a new conserved family of ring-finger proteins. Genetics 155:1231–1244.
Ahmad, F.J., and Baas, P.W. (1995). Microtubules released from the neuronal centrosome are transported into the axon. J. Cell Sci. 108:2761–2769.
Allen, S., Heath, P.R., Kirby, J., Wharton, S.B., Cookson, M.R., Menzies, F.M., Banks, R.E., and Shaw, P.J. (2003). Analysis of the cytosolic proteome in a cell culture model of familial amyotrophic lateral sclerosis reveals alterations to the proteasome, antioxidant defenses, and nitric oxide synthetic pathways. J. Biol. Chem. 278:6371–6383.
Ambrose, C.M., Duyao, M.P., Barnes, G., Bates, G.P., Lin, C.S., Srinidhi, J., Baxendale, S., Hummerich, H., Lehrach, H., and Altherr, M. (1994). Structure and expression of the Huntington’s disease gene: evidence against simple inactivation due to an expanded CAG repeat. Somat. Cell Mol. Genet. 20:27–38.
Amerik, A., Swaminathan, S., Krantz, B.A., Wilkinson, K.D., and Hochstrasser, M. (1997). In vivo disassembly of free polyubiquitin chains by yeast Ubp14 modulates rates of protein degradation by the proteasome. EMBO J. 16:4826–4838.
Andersen, S.S. (1999). Molecular characteristics of the centrosome. Int. Rev. Cytol. 187:51–109.
Ardley, H.C., Scott, G.B., Rose, S.A., Tan, N.G., Markham, A.F., and Robinson, P.A. (2003). Inhibition of proteasomal activity causes inclusion formation in neuronal and non-neuronal cells overexpressing Parkin. Mol. Biol. Cell 14:4541–4556.
Baas, P.W. (2002). Neuronal polarity: microtubules strike back [comment]. Nat. Cell Biol. 4:E194–E195.
Banchereau, J., and Steinman, R.M. (1998). Dendritic cells and the control of immunity. Nature 392:245–252.
Bardag-Gorce, F., Riley, N., Nguyen, V., Montgomery, R.O., French, B.A., Li, J., van Leeuwen, F.W., Lungo, W., McPhaul, L.W., and French, S.W. (2003). The mechanism of cytokeratin aggresome formation: the role of mutant ubiquitin (UBB+1). Exp. Mol. Pathol. 74:160–167.
Bedford, F.K., Kittler, J.T., Muller, E., Thomas, P., Uren, J.M., Merlo, D., Wisden, W., Triller, A., Smart, T.G., and Moss, S.J. (2001). GABA(A) receptor cell surface number and subunit stability are regulated by the ubiquitin-like protein Plic-1. Nat. Neurosci. 4:908–916.
Benaroudj, N., Zwickl, P., Seemuller, E., Baumeister, W., and Goldberg, A.L. (2003). ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation [see comment]. Mol. Cell 11:69–78.
Bence, N.F., Sampat, R.M., and Kopito, R.R. (2001). Impairment of the ubiquitin-proteasome system by protein aggregation [see comment]. Science 292:1552–1555.
Bennett, M.C., Bishop, Y.L., Chock, P.B., Chase, T.N., and Mouradian, M.M. (1999). Degradation of a-synuclein by proteasome. J. Biol. Chem. 274:33855–33858.
Bennett, M.J., Huey-Tubman, K.E., Herr, A.B., West, A.P., Jr., Ross, S.A., and Bjorkman, P.J. (2002). Inaugural article: a linear lattice model for polyglutamine in CAG-expansion diseases. Proc. Natl. Acad. Sci. USA 99:11634–11639.
Bermak, J.C., and Zhou, Q.Y. (2001). Accessory proteins in the biogenesis of G protein-coupled receptors. Mol. Intervent. 1:282–287.
Berry, V., Mackay, D., Khaliq, S., Francis, P.J., Hameed, A., Anwar, K., Mehdi, S.Q., Newbold, R.J., Ionides, A., Shiels, A., Moore, T., and Bhattacharya, S.S. (1999). Connexin 50 mutation in a family with congenital “zonular nuclear” pulverulent cataract of Pakistani origin. Hum. Genet. 105:168–170.
Berthoud, V.M., Minogue, P.J., Guo, J., Williamson, E.K., Xu, X., Ebihara, L., and Beyer, E.C. (2003). Loss of function and impaired degradation of a cataract-associated mutant connexin50. Eur. J. Cell Biol. 82:209–221.
Biasini, E., Fioriti, L., Ceglia, I., Invernizzi, R., Bertoli, A., Chiesa, R., and Forloni, G. (2004). Proteasome inhibition and aggregation in Parkinson’s disease: a comparative study in untransfected and transfected cells. J. Neurochem. 88:545–553.
Bonifati, V., De Michele, G., Lucking, C.B., Durr, A., Fabrizio, E., Ambrosio, G., Vanacore, N., De Mari, M., Marconi, R., Capus, L., Breteler, M.M., Gasser, T., Oostra, B., Wood, N., Agid, Y., Filla, A., Meco, G., Brice, A., and Italian Pd Genetics Study Group, French PD Genetics Study Group and the European Consortium on genetic susceptibility in Parkinson’s Disease. (2001). The parkin gene and its phenotype. Neurol. Sci. 22:51–52.
Borchelt, D.R., Lee, M.K., Slunt, H.S., Guarnieri, M., Xu, Z.S., Wong, P.C., Brown, R.H., Jr., Price, D.L., Sisodia, S.S., and Cleveland, D.W. (1994). Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc. Natl. Acad. Sci. USA 91:8292–8296.
Borchelt, D.R., Guarnieri, M., Wong, P.C., Lee, M.K., Slunt, H.S., Xu, Z.S., Sisodia, S.S., Price, D.L., and Cleveland, D.W. (1995). Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild-type subunit function. J. Biol. Chem. 270:3234–3238.
Borges, K., and Dingledine, R. (1998). AMPA receptors: molecular and functional diversity. Prog. Brain Res. 116:153–170.
Braun, B.C., Glickman, M., Kraft, R., Dahlmann, B., Kloetzel, P.M., Finley, D., and Schmidt, M. (1999). The base of the proteasome regulatory particle exhibits chaperone-like activity. Nat. Cell Biol. 1:221–226.
Brion, J.P., and Couck, A.M. (1995). Cortical and brainstem-type Lewy bodies are immunoreactive for the cyclindependent kinase 5. Am. J. Pathol. 147:1465–1476.
Brooks, P., Fuertes, G., Murray, R.Z., Bose, S., Knecht, E., Rechsteiner, M.C., Hendil, K.B., Tanaka, K., Dyson, J., and Rivett, J. (2000). Subcellular localization of proteasomes and their regulatory complexes in mammalian cells. Biochem. J. 346 (Pt 1):155–161.
Bruijn, L.I., and Cleveland, D.W. (1996). Mechanisms of selective motor neuron death in ALS: insights from transgenic mouse models of motor neuron disease. Neuropathol. Appl. Neurobiol. 22:373–387.
Bulteau, A.L., Lundberg, K.C., Humphries, K.M., Sadek, H.A., Szweda, P.A., Friguet, B., and Szweda, L.I. (2001). Oxidative modification and inactivation of the proteasome during coronary occlusion/reperfusion. J. Biol. Chem. 276:30057–30063.
Burbea, M., Dreier, L., Dittman, J.S., Grunwald, M.E., and Kaplan, J.M. (2002). Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans. Neuron 35:107–120.
Burkhardt, J.K., Echeverri, C.J., Nilsson, T., and Vallee, R.B. (1997). Overexpression of the dynamitin (p50) subunit of the dynactin complex disrupts dynein-dependent maintenance of membrane organelle distribution. J. Cell Biol. 139:469–484.
Campbell, D.S., and Holt, C.E. (2001). Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation [see comment]. Neuron 32:1013–1026.
Carrard, G., Bulteau, A.L., Petropoulos, I., and Friguet, B. (2002). Impairment of proteasome structure and function in aging. Int. J. Biochem. Cell Biol. 34:1461–1474.
Chavez Zobel, A.T., Loranger, A., Marceau, N., Theriault, J.R., Lambert, H., and Landry, J. (2003). Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G alphaB-crystallin mutant. Hum. Mol. Genet. 12:1609–1620.
Chen, M., Goorha, R., and Murti, K.G. (1986). Interaction of frog virus 3 with the cytomatrix. IV. Phosphorylation of vimentin precedes the reorganization of intermediate filaments around the virus assembly sites. J. Gen. Virol. 67:915–922.
Chou, Y.H., Ngai, K.L., and Goldman, R. (1991). The regulation of intermediate filament reorganization in mitosis. p34cdc2 phosphorylates vimentin at a unique N-terminal site. J. Biol. Chem. 266:7325–7328.
Chou, Y.H., Khuon, S., Herrmann, H., and Goldman, R.D. (2003). Nestin promotes the phosphorylation-dependent disassembly of vimentin intermediate filaments during mitosis. Mol. Biol. Cell 14:1468–1478.
Ciechanover, A. (1998). The ubiquitin-proteasome pathway: on protein death and cell life. EMBO J. 17:7151–7160.
Cleveland, D.W., Bruijn, L.I., Wong, P.C., Marszalek, J.R., Vechio, J.D., Lee, M.K., Xu, X.S., Borchelt, D.R., Sisodia, S.S., and Price, D.L. (1996). Mechanisms of selective motor neuron death in transgenic mouse models of motor neuron disease. Neurology 47:S54–S61 [discussion S61–S2].
Cohen, E., and Taraboulos, A. (2003). Scrapie-like prion protein accumulates in aggresomes of cyclosporin A-treated cells. EMBO J. 22:404–417.
Colledge, M., Snyder, E.M., Crozier, R.A., Soderling, J.A., Jin, Y., Langeberg, L.K., Lu, H., Bear, M.F., and Scott, J.D. (2003). Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron 40:595–607.
Conaway, R.C., Brower, C.S., and Conaway, J.W. (2002). Emerging roles of ubiquitin in transcription regulation. Science 296:1254–1258.
Corti, O., Hampe, C., Koutnikova, H., Darios, F., Jacquier, S., Prigent, A., Robinson, J.C., Pradier, L., Ruberg, M., Mirande, M., Hirsch, E., Rooney, T., Fournier, A., and Brice, A. (2003). The p38 subunit of the aminoacyl-tRNA synthetase complex is a Parkin substrate: linking protein biosynthesis and neurodegeneration. Hum. Mol. Genet. 12:1427–1437.
Craig, K.L., and Tyers, M. (1999). The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction. Prog. Biophys. Mol. Biol. 72:299–328.
Czar, M.J., Lyons, R.H., Welsh, M.J., Renoir, J.M., and Pratt, W.B. (1995). Evidence that the FK506-binding immunophilin heat shock protein 56 is required for trafficking of the glucocorticoid receptor from the cytoplasm to the nucleus. Mol. Endocrinol. 9:1549–1560.
Dangond, F., Hwang, D., Camelo, S., Pasinelli, P., Frosch, M.P., Stephanopoulos, G., Brown, R.H., Jr., and Gullans, S.R. (2004). Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter. Physiol. Genom. 16:229–239.
Dantuma, N.P., Lindsten, K., Glas, R., Jellne, M., and Masucci, M.G. (2000). Short-lived green fluorescent proteins for quantifying ubiquitin/proteasome-dependent proteolysis in living cells [see comment]. Nat. Biotechnol. 18:538–543.
Dauer, W., and Przedborski, S. (2003). Parkinson’s disease: mechanisms and models. Neuron 39:889–909.
Davidson, W.S., Jonas, A., Clayton, D.F., and George, J.M. (1998). Stabilization of alpha-synuclein secondary structure upon binding to synthetic membranes. J. Biol. Chem. 273:9443–9449.
Demand, J., Alberti, S., Patterson, C., and Hohfeld, J. (2001). Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling [see comment]. Curr. Biol. 11:1569–1577.
den Engelsman, J., Keijsers, V., de Jong, W.W., and Boelens, W.C. (2003). The small heat-shock protein alpha B-crystallin promotes FBX4-dependent ubiquitination. J. Biol. Chem. 278:4699–4704.
Desai, A., and Mitchison, T.J. (1997). Microtubule polymerization dynamics. Annu. Rev. Cell Dev. Biol. 13:83–117.
Deshaies, R.J. (1999). SCF and Cullin/ring H2-based ubiquitin ligases. Annu. Rev. Cell Dev. Biol. 15:435–467.
Deveraux, Q., Ustrell, V., Pickart, C., and Rechsteiner, M. (1994). A 26S protease subunit that binds ubiquitin conjugates. J. Biol. Chem. 269:7059–7061.
DiAntonio, A., Haghighi, A.P., Portman, S.L., Lee, J.D., Amaranto, A.M., and Goodman, C.S. (2001). Ubiquitinationdependent mechanisms regulate synaptic growth and function. Nature 412:449–452.
Dingledine, R., Borges, K., Bowie, D., and Traynelis, S.F. (1999). The glutamate receptor ion channels. Pharmacol. Rev. 51:7–61.
Dinudom, A., Harvey, K.F., Komwatana, P., Young, J.A., Kumar, S., and Cook, D.I. (1998). Nedd4 mediates control of an epithelial Na+ channel in salivary duct cells by cytosolic Na+. Proc. Natl. Acad. Sci. USA 95:7169–7173.
Donaldson, K.M., Li, W., Ching, K.A., Batalov, S., Tsai, C.C., and Joazeiro, C.A. (2003). Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc. Natl. Acad. Sci. USA 100:8892–8897.
Dryja, T.P., McGee, T.L., Reichel, E., Hahn, L.B., Cowley, G.S., Yandell, D.W., Sandberg, M.A., and Berson, E.L. (1990). A point mutation of the rhodopsin gene in one form of retinitis pigmentosa. Nature 343:364–366.
Dryja, T.P., Hahn, L.B., Cowley, G.S., McGee, T.L., and Berson, E.L. (1991). Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. USA 88:9370–9374.
Dunn, R., Klos, D.A., Adler, A.S., and Hicke, L. (2004). The C2 domain of the Rsp5 ubiquitin ligase binds membrane phosphoinositides and directs ubiquitination of endosomal cargo. J. Cell Biol. 165:135–144.
Ehlers, M.D. (2003). Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nat. Neurosci. 6:231–242.
Eichenbaum, H. (1995). Spatial learning. The LTP-memory connection. Nature 378:131–132.
Eliezer, D., Kutluay, E., Bussell, R., Jr., and Browne, G. (2001). Conformational properties of alpha-synuclein in its free and lipid-associated states. J. Mol. Biol. 307:1061–1073.
Fabunmi, R.P., Wigley, W.C., Thomas, P.J., and DeMartino, G.N. (2000). Activity and regulation of the centrosomeassociated proteasome. J. Biol. Chem. 275:409–413.
Fink, A.L. (1999). Chaperone-mediated protein folding. Physiol. Rev. 79:425–449.
Finley, D., Bartel, B., and Varshavsky, A. (1989). The tails of ubiquitin precursors are ribosomal proteins whose fusion to ubiquitin facilitates ribosome biogenesis. Nature 338:394–401.
Flannery, J.G., Farber, D.B., Bird, A.C., and Bok, D. (1989). Degenerative changes in a retina affected with autosomal dominant retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 30:191–211.
Fornai, F., Lenzi, P., Gesi, M., Ferrucci, M., Lazzeri, G., Busceti, C.L., Ruffoli, R., Soldani, P., Ruggieri, S., Alessandri, M.G., and Paparelli, A. (2003). Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition. J. Neurosci. 23:8955–8966.
Foroud, T., Uniacke, S.K., Liu, L., Pankratz, N., Rudolph, A., Halter, C., Shults, C., Marder, K., Conneally, P.M., Nichols, W.C., and Parkinson Study Group. (2003). Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Neurology 60:796–801.
French, B.A., van Leeuwen, F., Riley, N.E., Yuan, Q.X., Bardag-Gorce, F., Gaal, K., Lue, Y.H., Marceau, N., and French, S.W. (2001). Aggresome formation in liver cells in response to different toxic mechanisms: role of the ubiquitin-proteasome pathway and the frameshift mutant of ubiquitin. Exp. Mol. Pathol. 71:241–246.
Fuchs, S.Y., Spiegelman, V.S., and Kumar, K.G. (2004). The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer. Oncogene 23:2028–2036.
Gai, W.P., Power, J.H., Blumbergs, P.C., Culvenor, J.G., and Jensen, P.H. (1999). Alpha-synuclein immunoisolation of glial inclusions from multiple system atrophy brain tissue reveals multiprotein components. J. Neurochem. 73:2093–2100.
Gai, W.P., Yuan, H.X., Li, X.Q., Power, J.T., Blumbergs, P.C., and Jensen, P.H. (2000). In situ and in vitro study of colocalization and segregation of alpha-synuclein, ubiquitin, and lipids in Lewy bodies. Exp. Neurol. 166:324–333.
Gai, W.P., Pountney, D.L., Power, J.H., Li, Q.X., Culvenor, J.G., McLean, C.A., Jensen, P.H., and Blumbergs, P.C. (2003). alpha-Synuclein fibrils constitute the central core of oligodendroglial inclusion filaments in multiple system atrophy. Exp. Neurol. 181:68–78.
Galigniana, M.D., Radanyi, C., Renoir, J.M., Housley, P.R., and Pratt, W.B. (2001). Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus. J. Biol. Chem. 276:14884–14889.
Ganesh, S., Delgado-Escueta, A.V., Suzuki, T., Francheschetti, S., Riggio, C., Avanzini, G., Rabinowicz, A., Bohlega, S., Bailey, J., Alonso, M.E., Rasmussen, A., Thomson, A.E., Ochoa, A., Prado, A.J., Medina, M.T., and Yamakawa, K. (2002). Genotype-phenotype correlations for EPM2A mutations in Lafora’s progressive myoclonus epilepsy: exon 1 mutations associate with an early-onset cognitive deficit subphenotype. Hum. Mol. Genet. 11:1263–1271.
Garcia-Mata, R., Bebok, Z., Sorscher, E.J., and Sztul, E.S. (1999). Characterization and dynamics of aggresome formation by a cytosolic GFP-chimera. J. Cell Biol. 146:1239–1254.
Gasser, T. (2001). Genetics of Parkinson’s disease. J. Neurol. 248:833–840.
Glover, J.R., and Lindquist, S. (1998). Hsp104, Hsp70, and Hsp40: a novel chaperone system that rescues previously aggregated proteins. Cell 94:73–82.
Goldfarb, L.G., Park, K.Y., Cervenakova, L., Gorokhova, S., Lee, H.S., Vasconcelos, O., Nagle, J.W., Semino-Mora, C., Sivakumar, K., and Dalakas, M.C. (1998). Missense mutations in desmin associated with familial cardiac and skeletal myopathy. Nat. Genet. 19:402–403.
Goldfarb, L.G., Vicart, P., Goebel, H.H., and Dalakas, M.C. (2004). Desmin myopathy. Brain 127:723–734.
Goldman, R.D., Chou, Y.H., Prahlad, V., and Yoon, M. (1999). Intermediate filaments: dynamic processes regulating their assembly, motility, and interactions with other cytoskeletal systems. FASEB J. 13(Suppl 2):S261–S265.
Goldstein, L.S., and Yang, Z. (2000). Microtubule-based transport systems in neurons: the roles of kinesins and dyneins. Annu. Rev. Neurosci. 23:39–71.
Gong, X., Li, E., Klier, G., Huang, Q., Wu, Y., Lei, H., Kumar, N.M., Horwitz, J., and Gilula, N.B. (1997). Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91:833–843.
Goodenough, D.A. (1992). The crystalline lens. A system networked by gap junctional intercellular communication. Semin. Cell Biol. 3:49–58.
Goodenough, D.A., Goliger, J.A., and Paul, D.L. (1996). Connexins, connexons, and intercellular communication. Annu. Rev. Biochem. 65:475–502.
Gorrie, G.H., Vallis, Y., Stephenson, A., Whitfield, J., Browning, B., Smart, T.G., and Moss, S.J. (1997). Assembly of GABAA receptors composed of alpha1 and beta2 subunits in both cultured neurons and fibroblasts. J. Neurosci. 17:6587–6596.
Grant, P., Sharma, P., and Pant, H.C. (2001). Cyclin-dependent protein kinase 5 (Cdk5) and the regulation of neurofilament metabolism. Eur. J. Biochem. 268:1534–1546.
Gray, D.A., Tsirigotis, M., and Woulfe, J. (2003). Ubiquitin, proteasomes, and the aging brain. Sci. Aging Knowl. Environ. 2003:RE6.
Groll, M., Bajorek, M., Kohler, A., Moroder, L., Rubin, D.M., Huber, R., Glickman, M.H., and Finley, D. (2000). A gated channel into the proteasome core particle [see comment]. Nat. Struct. Biol. 7:1062–1067.
Gu, W.J., Corti, O., Araujo, F., Hampe, C., Jacquier, S., Lucking, C.B., Abbas, N., Duyckaerts, C., Rooney, T., Pradier, L., Ruberg, M., and Brice, A. (2003). The C289G and C418R missense mutations cause rapid sequestration of human Parkin into insoluble aggregates. Neurobiol. Dis. 14:357–364.
Gurney, M.E. (1994). Transgenic-mouse model of amyotrophic lateral sclerosis[comment]. N. Engl. J. Med. 331:1721–1722.
Gurney, M.E. (2000). What transgenic mice tell us about neurodegenerative disease. Bioessays 22:297–304.
Gutekunst, C.A., Li, S.H., Yi, H., Ferrante, R.J., Li, X.J., and Hersch, S.M. (1998). The cellular and subcellular localization of huntingtin-associated protein 1 (HAP1): comparison with huntingtin in rat and human. J. Neurosci. 18:7674–7686.
Gutekunst, C.A., Li, S.H., Yi, H., Mulroy, J.S., Kuemmerle, S., Jones, R., Rye, D., Ferrante, R.J., Hersch, S.M., and Li, X.J. (1999). Nuclear and neuropil aggregates in Huntington’s disease: relationship to neuropathology. J. Neurosci. 19:2522–2534.
Hansson, O., Petersen, A., Leist, M., Nicotera, P., Castilho, R.F., and Brundin, P. (1999). Transgenic mice expressing a Huntington’s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. Proc. Natl. Acad. Sci. USA 96:8727–8732.
Harada, M., Sakisaka, S., Terada, K., Kimura, R., Kawaguchi, T., Koga, H., Kim, M., Taniguchi, E., Hanada, S., Suganuma, T., Furuta, K., Sugiyama, T., and Sata, M. (2001). A mutation of the Wilson disease protein, ATP7B, is degraded in the proteasomes and forms protein aggregates [comment]. Gastroenterology 120:967–974.
Harper, P.S. (1991). Huntington’s disease. London: W.B. Saunders.
Harris, W.A., and Holt, C.E. (1999). Neurobiology. Slit, the midline repellent. Nature 398:462–463.
Hatakeyama, S., and Nakayama, K.I. (2003). U-box proteins as a new family of ubiquitin ligases. Biochem. Biophys. Res. Commun. 302:635–645.
Hattori, N., Shimura, H., Kubo, S., Wang, M., Shimizu, N., Tanaka, K., and Mizuno, Y. (2000). Importance of familial Parkinson’s disease and parkinsonism to the understanding of nigral degeneration in sporadic Parkinson’s disease. J. Neural Trans. Suppl.:101–116.
Heath, C.M., Windsor, M., and Wileman, T. (2001). Aggresomes resemble sites specialized for virus assembly. J. Cell Biol. 153:449–455.
Hegde, A.N., and DiAntonio, A. (2002). Ubiquitin and the synapse. Nat. Rev. Neurosci. 3:854–861.
Hegde, A.N., Inokuchi, K., Pei, W., Casadio, A., Ghirardi, M., Chain, D.G., Martin, K.C., Kandel, E.R., and Schwartz, J.H. (1997). Ubiquitin C-terminal hydrolase is an immediate-early gene essential for long-term facilitation in Aplysia. Cell 89:115–126.
Hershko, A., and Ciechanover, A. (1998). The ubiquitin system. Annu. Rev. Biochem. 67:425–479.
Hershko, A., Ciechanover, A., and Varshavsky, A. (2000). Basic Medical Research Award. The ubiquitin system. Nat. Med. 6:1073–1081.
Hicke, L., and Dunn, R. (2003). Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Annu. Rev. Cell Dev. Biol. 19:141–172.
Hishikawa, N., Niwa, J., Doyu, M., Ito, T., Ishigaki, S., Hashizume, Y., and Sobue, G. (2003). Dorfin localizes to the ubiquitylated inclusions in Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy, and amyotrophic lateral sclerosis. Am. J. Pathol. 163:609–619.
Hoffman, E.K., Wilcox, H.M., Scott, R.W., and Siman, R. (1996). Proteasome inhibition enhances the stability of mouse Cu/Zn superoxide dismutase with mutations linked to familial amyotrophic lateral sclerosis. J. Neurol. Sci. 139:15–20.
Holcombe, H., Mellman, I., Janeway, C.A., Jr., Bottomly, K., and Dittel, B.N. (2002). The immunosuppressive agent 15-deoxyspergualin functions by inhibiting cell cycle progression and cytokine production following naive T cell activation. J. Immunol. 169:4982–4989.
Horwich, A. (2002). Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions. J. Clin. Invest. 110:1221–1232.
Howland, D.S., Liu, J., She, Y., Goad, B., Maragakis, N.J., Kim, B., Erickson, J., Kulik, J., DeVito, L., Psaltis, G., DeGennaro, L.J., Cleveland, D.W., and Rothstein, J.D. (2002). Focal loss of the glutamate transporter EAAT2 in a transgenic rat model of SOD1 mutant-mediated amyotrophic lateral sclerosis (ALS). Proc. Natl. Acad. Sci. USA 99:1604–1609.
Huang, Y., Baker, R.T., and Fischer-Vize, J.A. (1995). Control of cell fate by a deubiquitinating enzyme encoded by the fat facets gene. Science 270:1828–1831.
Huang, Y.Y., Nguyen, P.V., Abel, T., and Kandel, E.R. (1996). Long-lasting forms of synaptic potentiation in the mammalian hippocampus. Learn. Mem. 3:74–85.
Hubbert, C., Guardiola, A., Shao, R., Kawaguchi, Y., Ito, A., Nixon, A., Yoshida, M., Wang, X.F., and Yao, T.P. (2002). HDAC6 is a microtubule-associated deacetylase [see comment]. Nature 417:455–458.
Huh, K.H., and Wenthold, R.J. (1999). Turnover analysis of glutamate receptors identifies a rapidly degraded pool of the N-methyl-D-aspartate receptor subunit, NR1, in cultured cerebellar granule cells. J. Biol. Chem. 274:151–157.
Hyun, D.H., Lee, M., Halliwell, B., and Jenner, P. (2003). Proteasomal inhibition causes the formation of protein aggregates containing a wide range of proteins, including nitrated proteins. J. Neurochem. 86:363–373.
Illing, M.E., Rajan, R.S., Bence, N.F., and Kopito, R.R. (2002). A rhodopsin mutant linked to autosomal dominant retinitis pigmentosa is prone to aggregate and interacts with the ubiquitin proteasome system. J. Biol. Chem. 277:34150–34160.
Imai, Y., Soda, M., and Takahashi, R. (2000). Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J. Biol. Chem. 275:35661–35664.
Imai, Y., Soda, M., Hatakeyama, S., Akagi, T., Hashikawa, T., Nakayama, K.I., and Takahashi, R. (2002). CHIP is associated with Parkin, a gene responsible for familial Parkinson’s disease, and enhances its ubiquitin ligase activity. Mol. Cell 10:55–67.
Ingano, L.A., Lentini, K.M., Kovacs, I., Tanzi, R.E., and Kovacs, D.M. (2000). Cytoplasmic presenilin aggregates in proteasome inhibitor-treated cells. Ann. N Y Acad. Sci. 920:259–260.
Ingham, R.J., Gish, G., and Pawson, T. (2004). The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture. Oncogene 23:1972–1984.
Ito, H., Okamoto, K., Nakayama, H., Isobe, T., and Kato, K. (1997). Phosphorylation of alphaB-crystallin in response to various types of stress. J. Biol. Chem. 272:29934–29941.
Ito, H., Kamei, K., Iwamoto, I., Inaguma, Y., Garcia-Mata, R., Sztul, E., and Kato, K. (2002). Inhibition of proteasomes induces accumulation, phosphorylation, and recruitment of HSP27 and alphaB-crystallin to aggresomes. J. Biochem. 131:593–603.
Ito, H., Kamei, K., Iwamoto, I., Inaguma, Y., Tsuzuki, M., Kishikawa, M., Shimada, A., Hosokawa, M., and Kato, K. (2003). Hsp27 suppresses the formation of inclusion bodies induced by expression of R120G alpha B-crystallin, a cause of desmin-related myopathy. Cell. Mol. Life Sci. 60:1217–1223.
Jaakkola, P., Mole, D.R., Tian, Y.M., Wilson, M.I., Gielbert, J., Gaskell, S.J., Kriegsheim, A., Hebestreit, H.F., Mukherji, M., Schofield, C.J., Maxwell, P.H., Pugh, C.W., and Ratcliffe, P.J. (2001). Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation [see comment]. Science 292:468–472.
Jesenberger, V., and Jentsch, S. (2002). Deadly encounter: ubiquitin meets apoptosis. Nat. Rev. Mol. Cell Biol. 3:112–121.
Jin, T., Gu, Y., Zanusso, G., Sy, M., Kumar, A., Cohen, M., Gambetti, P., and Singh, N. (2000). The chaperone protein BiP binds to a mutant prion protein and mediates its degradation by the proteasome. J. Biol. Chem. 275: 38699–38704.
Joazeiro, C.A., and Weissman, A.M. (2000). RING finger proteins: mediators of ubiquitin ligase activity. Cell 102:549–552.
Johnson, E.S., Bartel, B., Seufert, W., and Varshavsky, A. (1992). Ubiquitin as a degradation signal. EMBO J. 11:497–505.
Johnston, J.A., and Madura, K.I. (2004). Rings, chains and ladders: Ubiquitin goes to work in the neuron. Prog. Neurobiol. 73:227–257.
Johnston, J.A., Johnson, E.S., Waller, P.R., and Varshavsky, A. (1995). Methotrexate inhibits proteolysis of dihydrofolate reductase by the N-end rule pathway. J. Biol. Chem. 270:8172–8178.
Johnston, J.A., Ward, C.L., and Kopito, R.R. (1998). Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143:1883–1898.
Johnston, J.A., Dalton, M.J., Gurney, M.E., and Kopito, R.R. (2000). Formation of high molecular weight complexes of mutant Cu, Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 97:12571–12576.
Johnston, J.A., Illing, M.E., and Kopito, R.R. (2002). Cytoplasmic dynein/dynactin mediates the assembly of aggresomes. Cell Motil. Cytoskel. 53:26–38.
Jones, D., Crowe, E., Stevens, T.A., and Candido, E.P. (2002). Functional and phylogenetic analysis of the ubiquitylation system in Caenorhabditis elegans: ubiquitin-conjugating enzymes, ubiquitin-activating enzymes, and ubiquitin-like proteins. Genome Biol. 3:RESEARCH0002.
Kabore, A.F., Wang, W.J., Russo, S.J., and Beers, M.F. (2001). Biosynthesis of surfactant protein C: characterization of aggresome formation by EGFP chimeras containing propeptide mutants lacking conserved cysteine residues. J. Cell Sci. 114:293–302.
Kahns, S., Kalai, M., Jakobsen, L.D., Clark, B.F., Vandenabeele, P., and Jensen, P.H. (2003). Caspase-1 and caspase-8 cleave and inactivate cellular parkin. J. Biol. Chem. 278:23376–23380.
Kato, K., Ito, H., Kamei, K., Inaguma, Y., Iwamoto, I., and Saga, S. (1998). Phosphorylation of alphaB-crystallin in mitotic cells and identification of enzymatic activities responsible for phosphorylation. J. Biol. Chem. 273:28346–28354.
Kato, K., Ito, H., Kamei, K., and Iwamoto, I. (1999). Selective stimulation of Hsp27 and alphaB-crystallin but not Hsp70 expression by p38 MAP kinase activation. Cell Stress Chaperones 4:94–101.
Kaufman, R.J. (1999). Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13:1211–1233.
Kawaguchi, Y., Kovacs, J.J., McLaurin, A., Vance, J.M., Ito, A., and Yao, T.P. (2003). The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115:727–738.
Kawajiri, A., Yasui, Y., Goto, H., Tatsuka, M., Takahashi, M., Nagata, K., and Inagaki, M. (2003). Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase. Mol. Biol. Cell 14:1489–1500.
Kesavapany, S., Li, B.S., Amin, N., Zheng, Y.L., Grant, P., and Pant, H.C. (2004). Neuronal cyclin-dependent kinase 5: role in nervous system function and its specific inhibition by the Cdk5 inhibitory peptide. Biochim. Biophys. Acta 1697:143–153.
Kirby, J., Menzies, F.M., Cookson, M.R., Bushby, K., and Shaw, P.J. (2002). Differential gene expression in a cell culture model of SOD1-related familial motor neurone disease. Hum. Mol. Genet. 11:2061–2075.
Kisselev, A.F., Akopian, T.N., Castillo, V., and Goldberg, A.L. (1999). Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown. Mol. Cell 4:395–402.
Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., and Shimizu, N. (1998). Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism [see comment]. Nature 392:605–608.
Klemenz, R., Frohli, E., Steiger, R.H., Schafer, R., and Aoyama, A. (1991). Alpha B-crystallin is a small heat shock protein. Proc. Natl. Acad. Sci. USA 88:3652–3656.
Kloetzel, P.M. (2001). Antigen processing by the proteasome. Nat. Rev. Mol. Cell Biol. 2:179–187.
Koepp, D.M., Harper, J.W., and Elledge, S.J. (1999). How the cyclin became a cyclin: regulated proteolysis in the cell cycle. Cell 97:431–434.
Konietzko, U., Kauselmann, G., Scafidi, J., Staubli, U., Mikkers, H., Berns, A., Schweizer, M., Waltereit, R., and Kuhl, D. (1999). Pim kinase expression is induced by LTP stimulation and required for the consolidation of enduring LTP. EMBO J. 18:3359–3369.
Korlipara, L.V., and Schapira, A.H. (2002). Parkinson’s disease. Int. Rev. Neurobiol. 53:283–314.
Kostova, Z., and Wolf, D.H. (2003). For whom the bell tolls: protein quality control of the endoplasmic reticulum and the ubiquitin-proteasome connection. EMBO J. 22:2309–2317.
Kregel, K.C. (2002). Heat shock proteins: modifying factors in physiological stress responses and acquired thermotolerance. J. Appl. Physiol. 92:2177–2186.
Kruger, E., Kloetzel, P.M., and Enenkel, C. (2001). 20S proteasome biogenesis. Biochimie 83:289–293.
Kuusisto, E., Salminen, A., and Alafuzoff, I. (2001a). Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies. Neuroreport 12:2085–2090.
Kuusisto, E., Suuronen, T., and Salminen, A. (2001b). Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells. Biochem. Biophys. Res. Commun. 280:223–228.
Kuusisto, E., Parkkinen, L., and Alafuzoff, I. (2003). Morphogenesis of Lewy bodies: dissimilar incorporation of alphasynuclein, ubiquitin, and p62. J. Neuropathol. Exp. Neurol. 62:1241–1253.
Kuzuhara, S., Mori, H., Izumiyama, N., Yoshimura, M., and Ihara, Y. (1988). Lewy bodies are ubiquitinated. A light and electron microscopic immunocytochemical study. Acta Neuropathol. 75:345–353.
Kwak, S., Masaki, T., Ishiura, S., and Sugita, H. (1991). Multicatalytic proteinase is present in Lewy bodies and neurofi-brillary tangles in diffuse Lewy body disease brains. Neurosci. Lett. 128:21–24.
Lam, Y.A., Pickart, C.M., Alban, A., Landon, M., Jamieson, C., Ramage, R., Mayer, R.J., and Layfield, R. (2000). Inhibition of the ubiquitin-proteasome system in Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 97:9902–9906.
Lam, Y.A., Lawson, T.G., Velayutham, M., Zweier, J.L., and Pickart, C.M. (2002). A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal. Nature 416:763–767.
Lee, C., Schwartz, M.P., Prakash, S., Iwakura, M., and Matouschek, A. (2001). ATP-dependent proteases degrade their substrates by processively unraveling them from the degradation signal. Mol. Cell 7:627–637.
Lee, H.J., and Lee, S.J. (2002). Characterization of cytoplasmic alpha-synuclein aggregates. Fibril formation is tightly linked to the inclusion-forming process in cells. J. Biol. Chem. 277:48976–48983.
Lee, H.J., Shin, S.Y., Choi, C., Lee, Y.H., and Lee, S.J. (2002). Formation and removal of alpha-synuclein aggregates in cells exposed to mitochondrial inhibitors. J. Biol. Chem. 277:5411–5417.
Leggett, D.S., Hanna, J., Borodovsky, A., Crosas, B., Schmidt, M., Baker, R.T., Walz, T., Ploegh, H., and Finley, D. (2002). Multiple associated proteins regulate proteasome structure and function. Mol. Cell 10:495–507.
Lelouard, H., Gatti, E., Cappello, F., Gresser, O., Camosseto, V., and Pierre, P. (2002). Transient aggregation of ubiquitinated proteins during dendritic cell maturation. Nature 417:177–182.
Lelouard, H., Ferrand, V., Marguet, D., Bania, J., Camosseto, V., David, A., Gatti, E., and Pierre, P. (2004). Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins. J. Cell Biol. 164:667–675.
Leterrier, J.F., Kas, J., Hartwig, J., Vegners, R., and Janmey, P.A. (1996). Mechanical effects of neurofilament cross-bridges. Modulation by phosphorylation, lipids, and interactions with F-actin. J. Biol. Chem. 271:15687–15694.
Levitskaya, J., Sharipo, A., Leonchiks, A., Ciechanover, A., and Masucci, M.G. (1997). Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. Proc. Natl. Acad. Sci. USA 94:12616–12621.
Li, J., Uversky, V.N., and Fink, A.L. (2001). Effect of familial Parkinson’s disease point mutations A30P and A53T on the structural properties, aggregation, and fibrillation of human alpha-synuclein. Biochemistry 40:11604–11613.
Li, R., Zheng, Y., and Drubin, D.G. (1995). Regulation of cortical actin cytoskeleton assembly during polarized cell growth in budding yeast. J. Cell Biol. 128:599–615.
Li, S.H., Gutekunst, C.A., Hersch, S.M., and Li, X.J. (1998). Interaction of huntingtin-associated protein with dynactin P150Glued. J. Neurosci. 18:1261–12169.
Linden, D.J. (1999). The return of the spike: postsynaptic action potentials and the induction of LTP and LTD. Neuron 22:661–666.
Linden, D.J., and Connor, J.A. (1995). Long-term synaptic depression. Annu. Rev. Neurosci. 18:319–357.
Lindquist, S., and Kim, G. (1996). Heat-shock protein 104 expression is sufficient for thermotolerance in yeast. Proc. Natl. Acad. Sci. USA 93:5301–5306.
Lindsten, K., de Vrij, F.M., Verhoef, L.G., Fischer, D.F., van Leeuwen, F.W., Hol, E.M., Masucci, M.G., and Dantuma, N.P. (2002). Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation. J. Cell Biol. 157:417–427.
Lindsten, K., Menendez-Benito, V., Masucci, M.G., and Dantuma, N.P. (2003). A transgenic mouse model of the ubiquitin/proteasome system. Nat. Biotechnol. 21:897–902.
Lorick, K.L., Jensen, J.P., Fang, S., Ong, A.M., Hatakeyama, S., and Weissman, A.M. (1999). RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl. Acad. Sci. USA 96:11364–11369.
Luby-Phelps, K. (2000). Cytoarchitecture and physical properties of cytoplasm: volume, viscosity, diffusion, intracellular surface area. Int. Rev. Cytol. 192:189–221.
Lunkes, A., and Mandel, J.L. (1998). A cellular model that recapitulates major pathogenic steps of Huntington’s disease. Hum. Mol. Genet. 7:1355–1361.
Lupas, A., Koster, A.J., and Baumeister, W. (1993). Structural features of 26S and 20S proteasomes. Enzyme Protein 47:252–273.
Lupski, J.R., and Garcia, C.A. (2001). Charcot-marie-tooth peripheral neuropathies and related disorders. In: Scrivner, C., Beaudet, A., Valle, D., Sly, W., Childs, B., Kinzler, K., and Vogelstein, B. (eds.), The metabolic and molecular bases of inherited disease. New York: McGraw-Hill, pp. 5759–5788.
Ma, J., and Lindquist, S. (2001). Wild-type PrP and a mutant associated with prion disease are subject to retrograde transport and proteasome degradation. Proc. Natl. Acad. Sci. USA 98:14955–14960.
Ma, J., and Lindquist, S. (2002). Conversion of PrP to a self-perpetuating PrPSc-like conformation in the cytosol [see comment]. Science 298:1785–1788.
Ma, J., Wollmann, R., and Lindquist, S. (2002). Neurotoxicity and neurodegeneration when PrP accumulates in the cytosol [see comment]. Science 298:1781–1785.
Magin, T. M., Schroder, R., Leitgeb, S., Wanninger, F., Zatloukal, K., Grund, C., and Melton, D. W. (1998). Lessons from keratin 18 knockout mice: formation of novel keratin filaments, secondary loss of keratin 7 and accumulation of liver-specific keratin 8-positive aggregates. J. Cell Biol. 140:1441–1451.
Malinow, R., and Malenka, R.C. (2002). AMPA receptor trafficking and synaptic plasticity. Annu. Rev. Neurosci. 25:103–126.
Malone, C.J., Misner, L., Le Bot, N., Tsai, M.C., Campbell, J.M., Ahringer, J., and White, J.G. (2003). The C. elegans hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus. Cell 115:825–836.
Manganas, L.N., Akhtar, S., Antonucci, D.E., Campomanes, C.R., Dolly, J.O., and Trimmer, J.S. (2001). Episodic ataxia type-1 mutations in the Kv1.1 potassium channel display distinct folding and intracellular trafficking properties. J. Biol. Chem. 276:49427–49434.
Maniatis, T. (1999). A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless, and Hedgehog signaling pathways. Genes Dev. 13:505–510.
Maro, B. and Bornens, M. (1980). The centriole-nucleus association: effects of cytochalasine B and nocodozole. Biol. Cell 39:287–290.
Martin-Aparicio, E., Yamamoto, A., Hernandez, F., Hen, R., Avila, J., and Lucas, J.J. (2001). Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington’s disease. J. Neurosci. 21:8772–8781.
Martin-Aparicio, E., Avila, J., and Lucas, J.J. (2002). Nuclear localization of N-terminal mutant huntingtin is cell cycle dependent. Eur. J. Neurosci. 16:355–359.
Matsuoka, Y., Nishizawa, K., Yano, T., Shibata, M., Ando, S., Takahashi, T., and Inagaki, M. (1992). Two different protein kinases act on a different time schedule as glial filament kinases during mitosis. EMBO J. 11:2895–2902.
Matsuyama, A., Shimazu, T., Sumida, Y., Saito, A., Yoshimatsu, Y., Seigneurin-Berny, D., Osada, H., Komatsu, Y., Nishino, N., Khochbin, S., Horinouchi, S., and Yoshida, M. (2002). In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J. 21:6820–6831.
McCabe, B.D., Hom, S., Aberle, H., Fetter, R.D., Marques, G., Haerry, T.E., Wan, H., O’Connor, M.B., Goodman, C.S., and Haghighi, A.P. (2004). Highwire regulates presynaptic BMP signalling essential for synaptic growth. Neuron 41:891–905.
McNaught, K.S., Bjorklund, L.M., Belizaire, R., Isacson, O., Jenner, P., and Olanow, C.W. (2002a). Proteasome inhibition causes nigral degeneration with inclusion bodies in rats. Neuroreport 13:1437–1441.
McNaught, K.S., Mytilineou, C., Jnobaptiste, R., Yabut, J., Shashidharan, P., Jennert, P., and Olanow, C.W. (2002b). Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures. J. Neurochem. 81:301–306.
McNaught, K.S., Shashidharan, P., Perl, D.P., Jenner, P., and Olanow, C.W. (2002c). Aggresome-related biogenesis of Lewy bodies. Eur. J. Neurosci. 16:2136–2148.
McPhaul, L.W., Wang, J., Hol, E.M., Sonnemans, M.A., Riley, N., Nguyen, V., Yuan, Q.X., Lue, Y.H., Van Leeuwen, F.W., and French, S.W. (2002). Molecular misreading of the ubiquitin B gene and hepatic mallory body formation. Gastroenterology 122:1878–1885.
Meriin, A.B., Zhang, X., He, X., Newnam, G.P., Chernoff, Y.O., and Sherman, M.Y. (2002). Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1 [erratum appears in J. Cell Biol. 2002 Aug 5;158 (3):591]. J. Cell Biol. 157:997–1004.
Michalek, M.T., Grant, E.P., Gramm, C., Goldberg, A.L., and Rock, K.L. (1993). A role for the ubiquitin-dependent proteolytic pathway in MHC class I-restricted antigen presentation. Nature 363:552–554.
Milam, A.H., Li, Z.Y., and Fariss, R.N. (1998). Histopathology of the human retina in retinitis pigmentosa. Prog. Retinal Eye Res. 17:175–205.
Mishra, R.S., Bose, S., Gu, Y., Li, R., and Singh, N. (2003). Aggresome formation by mutant prion proteins: the unfolding role of proteasomes in familial prion disorders. J. Alzheimer’s Dis. 5:15–23.
Mitchison, T.J., and Kirschner, M.W. (1986). Isolation of mammalian centrosomes. Methods Enzymol. 134:261–268.
Mizushima, T., Hirao, T., Yoshida, Y., Lee, S.J., Chiba, T., Iwai, K., Yamaguchi, Y., Kato, K., Tsukihara, T., and Tanaka, K. (2004). Structural basis of sugar-recognizing ubiquitin ligase. Nat. Struct. Mol. Biol. 11:365–370.
Monia, B.P., Ecker, D.A., and Crooke, S.T. (1990). New perspectives on the structure and function of ubiquitin. Bio/Technology 8:209–215.
Moon, A., and Drubin, D.G. (1995). The ADF/cofilin proteins: stimulus-responsive modulators of actin dynamics. Mol. Biol. Cell 6:1423–1431.
Muchowski, P.J., Ning, K., D’Souza-Schorey, C., and Fields, S. (2002). Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment. Proc. Natl. Acad. Sci. USA 99: 727–732.
Muneoka, K.T., and Takigawa, M. (2003). 5-Hydroxytryptamine7 (5-HT7) receptor immunoreactivity-positive “stigmoid body”-like structure in developing rat brains. Int. J. Dev. Neurosci. 21:133–143.
Murakami, Y., Tanahashi, N., Tanaka, K., Omura, S., and Hayashi, S. (1996). Proteasome pathway operates for the degradation of ornithine decarboxylase in intact cells. Biochem. J. 317:77–80.
Murata, S., Minami, Y., Minami, M., Chiba, T.m and Tanaka, K. (2001). CHIP is a chaperone-dependent E3 ligase that ubiquitylates unfolded protein. EMBO Rep. 2:1133–1138.
Muresan, V. (2000). One axon, many kinesins: What’s the logic? J. Neurocytol. 29:799–818.
Muresan, V., Abramson, T., Lyass, A., Winter, D., Porro, E., Hong, F., Chamberlin, N.L., and Schnapp, B.J. (1998). KIF3C and KIF3A form a novel neuronal heteromeric kinesin that associates with membrane vesicles. Mol. Biol. Cell 9:637–652.
Murphey, R.K., and Godenschwege, T.A. (2002). New roles for ubiquitin in the assembly and function of neuronal circuits. Neuron 36:5–8.
Musil, L.S., Le, A.C., VanSlyke, J.K., and Roberts, L.M. (2000). Regulation of connexin degradation as a mechanism to increase gap junction assembly and function. J. Biol. Chem. 275:25207–25215.
Narayanan, V., and Scarlata, S. (2001). Membrane binding and self-association of alpha-synucleins. Biochemistry 40: 9927–9934.
Navon, A., and Goldberg, A.L. (2001). Proteins are unfolded on the surface of the ATPase ring before transport into the proteasome. Mol. Cell 8:1339–1350.
Okada, T., Ernst, O.P., Palczewski, K., and Hofmann, K.P. (2001). Activation of rhodopsin: new insights from structural and biochemical studies. Trends Biochem. Sci. 26:318–324.
Olsen, M.K., Roberds, S.L., Ellerbrock, B.R., Fleck, T.J., McKinley, D.K., and Gurney, M.E. (2001). Disease mechanisms revealed by transcription profiling in SOD1-G93A transgenic mouse spinal cord. Ann. Neurol. 50:730–740.
Ostrerova-Golts, N., Petrucelli, L., Hardy, J., Lee, J.M., Farer, M., and Wolozin, B. (2000). The A53T alpha-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20:6048–6054.
Pak, D.T., and Sheng, M. (2003). Targeted protein degradation and synapse remodeling by an inducible protein kinase. Science 302:1368–1373.
Pak, D.T., Yang, S., Rudolph-Correia, S., Kim, E., and Sheng, M. (2001). Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP [comment]. Neuron 31:289–303.
Pal, J.D., Berthoud, V.M., Beyer, E.C., Mackay, D., Shiels, A., and Ebihara, L. (1999). Molecular mechanism underlying a Cx50-linked congenital cataract [erratum appears in Am. J. Physiol. 1999 Dec;277 (6 Pt 1):section C]. Am. J. Physiol. 276:C1443–C1446.
Pareek, S., Notterpek, L., Snipes, G.J., Naef, R., Sossin, W., Laliberte, J., Iacampo, S., Suter, U., Shooter, E.M., and Murphy, R.A. (1997). Neurons promote the translocation of peripheral myelin protein 22 into myelin. J. Neurosci. 17:7754–7762.
Patil, C., and Walter, P. (2001). Intracellular signaling from the endoplasmic reticulum to the nucleus: the unfolded protein response in yeast and mammals. Curr. Opin. Cell Biol. 13:349–355.
Paxinou, E., Chen, Q., Weisse, M., Giasson, B.I., Norris, E.H., Rueter, S.M., Trojanowski, J.Q., Lee, V.M., and Ischiropoulos, H. (2001). Induction of alpha-synuclein aggregation by intracellular nitrative insult. J. Neurosci. 21:8053–8061.
Perutz, M.F., Johnson, T., Suzuki, M., and Finch, J.T. (1994). Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 21:5355–5358.
Petaja-Repo, U.E., Hogue, M., Laperriere, A., Bhalla, S., Walker, P., and Bouvier, M. (2001). Newly synthesized human delta opioid receptors retained in the endoplasmic reticulum are retrotranslocated to the cytosol, deglycosylated, ubiquitinated, and degraded by the proteasome. J. Biol. Chem. 276:4416–4423.
Piao, Y.S., Wakabayashi, K., Kakita, A., Yamada, M., Hayashi, S., Morita, T., Ikuta, F., Oyanagi, K., and Takahashi, H. (2003). Neuropathology with clinical correlations of sporadic amyotrophic lateral sclerosis: 102 autopsy cases examined between 1962 and 2000. Brain Pathol. 13:10–22.
Pickart, C.M. (2000). Ubiquitin in chains. Trends Biochem. Sci. 25:544–548.
Poeck, B., Fischer, S., Gunning, D., Zipursky, S.L., and Salecker, I. (2001). Glial cells mediate target layer selection of retinal axons in the developing visual system of Drosophila. Neuron 29:99–113.
Polyakov, A.V., Shagina, I.A., Khlebnikova, O.V., and Evgrafov, O.V. (2001). Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular pulverulent cataract. Clin. Genet. 60:476–478.
Polymeropoulos, M.H., Lavendan, C., Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, F., Stenroos, E.S., Chandraseknarappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R.C., DiIorio, G., Golbe, L.I., and Nussbaum, R.L. (1997). Mutation in the a-synuclein gene identified infamilies with Parkinson’s disease. Science 276:2045–2047.
Prusiner, S.B. (1998). The prion diseases. Brain Pathol. 8:499–513.
Prusiner, S.B., Scott, M.R., DeArmond, S.J., and Cohen, F.E. (1998). Prion protein biology. Cell 93:337–348.
Rajan, R.S., Illing, M.E., Bence, N.F., and Kopito, R.R. (2001). Specificity in intracellular protein aggregation and inclusion body formation. Proc. Natl. Acad. Sci. USA 98:13060–13065.
Rideout, H.J., Larsen, K.E., Sulzer, D., and Stefanis, L. (2001). Proteasomal inhibition leads to formation of ubiquitin/alpha-synuclein-immunoreactive inclusions in PC12 cells. J. Neurochem. 78:899–908.
Rieder, C.L., Faruki, S., and Khodjakov, A. (2001). The centrosome in vertebrates: more than a microtubule-organizing center. Trends Cell Biol. 11:413–419.
Riley, N.E., Bardag-Gorce, F., Montgomery, R.O., Li, J., Lungo, W., Lue, Y.H., and French, S.W. (2003). Microtubules are required for cytokeratin aggresome (Mallory body) formation in hepatocytes: an in vitro study. Exp. Mol. Pathol. 74:173–179.
Rock, K.L., and Goldberg, A.L. (1999). Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu. Rev. Immunol. 17:739–779.
Rock, K.L., Gramm, C., Rothstein, L., Clark, K., Stein, R., Dick, L., Hwang, D., and Goldberg, A.L. (1994). Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761–771.
Rosen, D.R., Siddique, T., Patterson, D., Figlewicz, D.A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O’Regan, J.P., and Deng, H.X. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis [see comment] [erratum appears in Nature 1993 Jul 22;364(6435):362; PMID: 8332197]. Nature 362:59–62.
Rubin, D.M., van Nocker, S., Glickman, M., Coux, O., Wefes, I., Sadis, S., Fu, H., Goldberg, A., Vierstra, R., and Finley, D. (1997). ATPase and ubiquitin-binding proteins of the yeast proteasome. Mol. Biol. Rep. 24:17–26.
Ryan, M.C., Shooter, E.M., and Notterpek, L. (2002). Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations. Neurobiol. Dis. 10:109–118.
Sakata, E., Yamaguchi, Y., Kurimoto, E., Kikuchi, J., Yokoyama, S., Yamada, S., Kawahara, H., Yokosawa, H., Hattori, N., Mizuno, Y., Tanaka, K., and Kato, K. (2003). Parkin binds the Rpn10 subunit of 26S proteasomes through its ubiquitin-like domain. EMBO Rep. 4:301–306.
Saliba, R.S., Munro, P.M., Luthert, P.J., and Cheetham, M.E. (2002). The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation. J. Cell Sci. 115:2907–2918.
Sampathu, D.M., Giasson, B.I., Pawlyk, A.C., Trojanowski, J.Q., and Lee, V.M. (2003). Ubiquitination of alpha-synuclein is not required for formation of pathological inclusions in alpha-synucleinopathies. Am. J. Pathol. 163:91–100.
Scherzinger, E., Sittler, A., Schweiger, K., Heiser, V., Lurz, R., Hasenbank, R., Bates, G.P., Lehrach, H., and Wanker, E.E. (1999). Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington’s disease pathology. Proc. Natl. Acad. Sci. USA 96:4604–4609.
Schiene-Fischer, C., and Yu, C. (2001). Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases. FEBS Lett. 495:1–6.
Schlossmacher, M.G., Frosch, M.P., Gai, W.P., Medina, M., Sharma, N., Forno, L., Ochiishi, T., Shimura, H., Sharon, R., Hattori, N., Langston, J.W., Mizuno, Y., Hyman, B.T., Selkoe, D.J., and Kosik, K.S. (2002). Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am. J. Pathol. 160:1655–1667.
Schreiber, S.L. (1991). Chemistry and biology of the immunophilins and their immunosuppressive ligands. Science 251: 283–287.
Sekimata, M., Tsujimura, K., Tanaka, J., Takeuchi, Y., Inagaki, N., and Inagaki, M. (1996). Detection of protein kinase activity specifically activated at metaphase-anaphase transition. J. Cell Biol. 132:635–641.
Semple, C.A., Group, R.G., and Members, G.S.L. (2003). The comparative proteomics of ubiquitination in mouse. Genome Res. 13:1389–1394.
Serrando, M., Casanovas, A., and Esquerda, J.E. (2002). Occurrence of glutamate receptor subunit 1-containing aggresome-like structures during normal development of rat spinal cord interneurons. J. Comp. Neurol. 442: 23–34.
Sharon, R., Goldberg, M.S., Bar-Josef, I., Betensky, R.A., Shen, J., and Selkoe, D.J. (2001). alpha-Synuclein occurs in lipid-rich high molecular weight complexes, binds fatty acids, and shows homology to the fatty acid-binding proteins. Proc. Natl. Acad. Sci. USA 98:9110–9115.
Shenoy, S.K., and Lefkowitz, R.J. (2003). Trafficking patterns of beta-arrestin and G protein-coupled receptors determined by the kinetics of beta-arrestin deubiquitination. J. Biol. Chem. 278:14498–14506.
Shenoy, S.K., McDonald, P.H., Kohout, T.A., and Lefkowitz, R.J. (2001). Regulation of receptor fate by ubiquitination of activated beta 2-adrenergic receptor and beta-arrestin. Science 294:1307–1313.
Sherman, M.Y., and Goldberg, A.L. (2001). Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29:15–32.
Shibata, N., Hirano, A., Kobayashi, M., Siddique, T., Deng, H.X., Hung, W.Y., Kato, T., and Asayama, K. (1996). Intense superoxide dismutase-1 immunoreactivity in intracytoplasmic hyaline inclusions of familial amyotrophic lateral sclerosis with posterior column involvement. J. Neuropathol. Exp. Neurol. 55:481–490.
Shiels, A., Mackay, D., Ionides, A., Berry, V., Moore, A., and Bhattacharya, S. (1998). A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant “zonular pulverulent” cataract, on chromosome 1q. Am. J. Hum. Genet. 62:526–532.
Shimura, H., Hattori, N., Kubo, S., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., and Suzuki, T. (2000). Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat. Genet. 25:302–305.
Shinoda, K. (1994). Sex-steroid receptor mechanism related to neuronal aromatase and the stigmoid body. Hormones Behav. 28:545–555.
Siddique, T., and Hentati, A. (1995). Familial amyotrophic lateral sclerosis. Clin. Neurosci. 3:338–347.
Silverstein, A.M., Galigniana, M.D., Kanelakis, K.C., Radanyi, C., Renoir, J.M., and Pratt, W.B. (1999). Different regions of the immunophilin FKBP52 determine its association with the glucocorticoid receptor, hsp90, and cytoplasmic dynein. J. Biol. Chem. 274:36980–36986.
Sitte, N., Merker, K., Von Zglinicki, T., Davies, K.J., and Grune, T. (2000a). Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part II—aging of nondividing cells. FASEB J. 14:2503–2510.
Sitte, N., Merker, K., Von Zglinicki, T., Grune, T., and Davies, K.J. (2000b). Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part I—effects of proliferative senescence. FASEB J. 14: 2495–2502.
Skalli, O., and Goldman, R.D. (1991). Recent insights into the assembly, dynamics, and function of intermediate filament networks. Cell Motil. Cytoskeleton 19:67–79.
Sloper-Mould, K.E., Jemc, J.C., Pickart, C.M., and Hicke, L. (2001). Distinct functional surface regions on ubiquitin. J. Biol. Chem. 276:30483–30489.
Spillantini, M.G., Schmidt, M.L., Lee, V.M., Trojanowski, J.Q., Jakes, R., and Goedert, M. (1997). Alpha-synuclein in Lewy bodies. Nature 388:839–840.
Spruck, C.H., and Strohmaier, H.M. (2002). Seek and destroy: SCF ubiquitin ligases in mammalian cell cycle control [see comment]. Cell Cycle 1:250–254.
Srinivasan, A.N., Nagineni, C.N., and Bhat, S.P. (1992). alpha A-crystallin is expressed in non-ocular tissues. J. Biol. Chem. 267:23337–23341.
Staropoli, J.F., McDermott, C., Martinat, C., Schulman, B., Demireva, E., and Abeliovich, A. (2003). Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity. Neuron 37:735–749.
Stephen, A.G., Trausch-Azar, J.S., Ciechanover, A., and Schwartz, A.L. (1996). The ubiquitin-activating enzyme E1 is phosphorylated and localized to the nucleus in a cell cycle-dependent manner. J. Biol. Chem. 271:15608–15614.
Steward, O., and Schuman, E.M. (2003). Compartmentalized synthesis and degradation of proteins in neurons. Neuron 40:347–359.
Stumptner, C., Heid, H., Fuchsbichler, A., Hauser, H., Mischinger, H.J., Zatloukal, K., and Denk, H. (1999). Analysis of intracytoplasmic hyaline bodies in a hepatocellular carcinoma. Demonstration of p62 as major constituent. Am. J. Pathol. 154:1701–1710.
Sun, D., Leung, C.L., and Liem, R.K. (1996). Phosphorylation of the high molecular weight neurofilament protein (NF-H). by Cdk5 and p35. J. Biol. Chem. 271:14245–14251.
Sung, C.H., Davenport, C.M., Hennessey, J.C., Maumenee, I.H., Jacobson, S.G., Heckenlively, J.R., Nowakowski, R., Fishman, G., Gouras, P., and Nathans, J. (1991a). Rhodopsin mutations in autosomal dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. USA 88:6481–6485.
Sung, C.H., Schneider, B.G., Agarwal, N., Papermaster, D.S., and Nathans, J. (1991b). Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. USA 88:8840–8844.
Sung, C.H., Davenport, C.M., and Nathans, J. (1993). Rhodopsin mutations responsible for autosomal dominant retinitis pigmentosa. Clustering of functional classes along the polypeptide chain. J. Biol. Chem. 268:26645–26649.
Tai, A.W., Chuang, J.Z., Bode, C., Wolfrum, U., and Sung, C.H. (1999). Rhodopsin’s carboxy-terminal cytoplasmic tail acts as a membrane receptor for cytoplasmic dynein by binding to the dynein light chain Tctex-1. Cell 97:877–887.
Tam, B.M., Moritz, O.L., Hurd, L.B., and Papermaster, D.S. (2000). Identification of an outer segment targeting signal in the COOH terminus of rhodopsin using transgenic Xenopus laevis. J. Cell Biol. 151:1369–1380.
Tanaka, M., Kim, Y.M., Lee, G., Junn, E., Iwatsubo, T., and Mouradian, M.M. (2004). Aggresomes formed by alpha-synuclein and synphilin-1 are cytoprotective. J. Biol. Chem. 279:4625–4631.
Tassin, A.M., and Bornens, M. (1999). Centrosome structure and microtubule nucleation in animal cells. Biol. Cell 91:343–354.
Taylor, J.P., Tanaka, F., Robitschek, J., Sandoval, C.M., Taye, A., Markovic-Plese, S., and Fischbeck, K.H. (2003). Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum. Mol. Genet. 12:749–757.
Tessier-Lavigne, M., and Goodman, C.S. (1996). The molecular biology of axon guidance. Science 274:1123–1133.
Thrower, J.S., Hoffman, L., Rechsteiner, M., and Pickart, C.M. (2000). Recognition of the polyubiquitin proteolytic signal. EMBO J. 19:94–102.
Tobler, A.R., Liu, N., Mueller, L., and Shooter, E.M. (2002). Differential aggregation of the Trembler and Trembler J mutants of peripheral myelin protein 22. Proc. Natl. Acad. Sci. USA 99:483–488.
Tofaris, G.K., Razzaq, A., Ghetti, B., Lilley, K.S., and Spillantini, M.G. (2003). Ubiquitination of alpha-synuclein in Lewy bodies is a pathological event not associated with impairment of proteasome function. J. Biol. Chem. 278:44405–44411.
Trimmer, P.A., Borland, M.K., Keeney, P.M., Bennett, J.P., Jr., and Parker, W.D., Jr. (2004). Parkinson’s disease transgenic mitochondrial cybrids generate Lewy inclusion bodies. J. Neurochem. 88:800–812.
Tsirigotis, M., Zhang, M., Chiu, R.K., Wouters, B.G., and Gray, D.A. (2001). Sensitivity of mammalian cells expressing mutant ubiquitin to protein-damaging agents. J. Biol. Chem. 276:46073–46078.
Turner, G.C., and Varshavsky, A. (2000). Detecting and measuring cotranslational protein degradation in vivo. Science 289:2117–2220.
Upadhya, S.C., and Hegde, A.N. (2003). A potential proteasome-interacting motif within the ubiquitin-like domain of parkin and other proteins. Trends Biochem. Sci. 28:280–283.
Vadlamudi, R.K., Joung, I., Strominger, J.L., and Shin, J. (1996). p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins. J. Biol. Chem. 271:20235–20237.
Valdeira, M.L., Bernardes, C., Cruz, B., and Geraldes, A. (1998). Entry of African swine fever virus into Vero cells and uncoating. Vet. Microbiol. 60:131–140.
Valentine, J.S., and Hart, P.J. (2003). Misfolded CuZnSOD and amyotrophic lateral sclerosis. Proc. Natl. Acad. Sci. USA 100:3617–3622.
Vallee, R.B., Williams, J.C., Varma, D., and Barnhart, L.E. (2004). Dynein: An ancient motor protein involved in multiple modes of transport. J. Neurobiol. 58:189–200.
van Leeuwen, F.W., Fischer, D.F., Benne, R., and Hol, E.M. (2000). Molecular misreading. A new type of transcript mutation in gerontology. Ann. N Y Acad. Sci. 908:267–281.
van Nocker, S., Sadis, S., Rubin, D.M., Glickman, M., Fu, H., Coux, O., Wefes, I., Finley, D., and Vierstra, R.D. (1996). 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. 16:6020–6028.
VanSlyke, J.K., and Musil, L.S. (2002). Dislocation and degradation from the ER are regulated by cytosolic stress. J. Cell Biol. 157:381–394.
VanSlyke, J.K., Deschenes, S.M., and Musil, L.S. (2000). Intracellular transport, assembly, and degradation of wild-type and disease-linked mutant gap junction proteins. Mol. Biol. Cell 11:1933–1946.
Varshavsky, A. (1997). The N-end rule pathway of protein degradation. Genes Cells 2:13–28.
Vicart, P., Caron, A., Guicheney, P., Li, Z., Prevost, M.C., Faure, A., Chateau, D., Chapon, F., Tome, F., Dupret, J.M., Paulin, D., and Fardeau, M. (1998). A missense mutation in the alphaB-crystallin chaperone gene causes a desminrelated myopathy. Nat. Genet. 20:92–95.
Waelter, S., Boeddrich, A., Lurz, R., Scherzinger, E., Lueder, G., Lehrach, H., and Wanker, E.E. (2001). Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell 12:1393–1407.
Wang, E.W., Kessler, B.M., Borodovsky, A., Cravatt, B.F., Bogyo, M., Ploegh, H.L., and Glas, R. (2000). Integration of the ubiquitin-proteasome pathway with a cytosolic oligopeptidase activity. Proc. Natl. Acad. Sci. USA 97:9990–9995.
Ward, C.L., Omura, S., and Kopito, R.R. (1995). Degradation of CFTR by the ubiquitin-proteasome pathway. Cell 83:121–127.
Wede, O.K., Lofgren, M., Li, Z., Paulin, D., and Arner, A. (2002). Mechanical function of intermediate filaments in arteries of different size examined using desmin deficient mice. J. Physiol. 540:941–949.
Wenzel, T., and Baumeister, W. (1995). Conformational constraints in protein degradation by the 20S proteasome. Nat. Struct. Biol. 2:199–204.
White, T.W., Goodenough, D.A., and Paul, D.L. (1998). Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts. J. Cell Biol. 143:815–825.
Wiederkehr, T., Bukau, B., and Buchberger, A. (2002). Protein turnover: a CHIP programmed for proteolysis [comment]. Curr. Biol. 12:R26–R28.
Wigley, W.C., Fabunmi, R.P., Lee, M.G., Marino, C.R., Muallem, S., DeMartino, G.N., and Thomas, P.J. (1999). Dynamic association of proteasomal machinery with the centrosome. J. Cell Biol. 145:481–490.
Wolfrum, U., and Schmitt, A. (2000). Rhodopsin transport in the membrane of the connecting cilium of mammalian photoreceptor cells. Cell Motil. Cytoskeleton 46:95–107.
Xu, J., Kao, S.Y., Lee, F.J., Song, W., Jin, L.W., and Yankner, B.A. (2002). Dopamine-dependent neurotoxicity of alphasynuclein: a mechanism for selective neurodegeneration in Parkinson disease [see comment]. Nat. Med. 8:600–606.
Yamamoto, A., Lucas, J.J., and Hen, R. (2000). Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease [see comment]. Cell 101:57–66.
Yedidia, Y., Horonchik, L., Tzaban, S., Yanai, A., and Taraboulos, A. (2001). Proteasomes and ubiquitin are involved in the turnover of the wild-type prion protein. EMBO J. 20:5383–5391.
Yin, Y., Manoury, B., and Fahraeus, R. (2003). Self-inhibition of synthesis and antigen presentation by Epstein-Barr virus-encoded EBNA1 [see comment]. Science 301:1371–1374.
Yoshida, Y., Chiba, T., Tokunaga, F., Kawasaki, H., Iwai, K., Suzuki, T., Ito, Y., Matsuoka, K., Yoshida, M., Tanaka, K., and Tai, T. (2002). E3 ubiquitin ligase that recognizes sugar chains. Nature 418:438–442.
Zanusso, G., Petersen, R.B., Jin, T., Jing, Y., Kanoush, R., Ferrari, S., Gambetti, P., and Singh, N. (1999). Proteasomal degradation and N-terminal protease resistance of the codon 145 mutant prion protein. J. Biol. Chem. 274:23396–23404.
Zatloukal, K., Stumptner, C., Lehner, M., Denk, H., Baribault, H., Eshkind, L.G., and Franke, W.W. (2000). Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies. Am. J. Pathol. 156:1263–1274.
Zatloukal, K., Stumptner, C., Fuchsbichler, A., Heid, H., Schnoelzer, M., Kenner, L., Kleinert, R., Prinz, M., Aguzzi, A., and Denk, H. (2002). p62 is a common component of cytoplasmic inclusions in protein aggregation diseases. Am. J. Pathol. 160:255–263.
Zeron, M.M., Chen, N., Moshaver, A., Lee, A.T., Wellington, C.L., Hayden, M.R., and Raymond, L.A. (2001). Mutant huntingtin enhances excitotoxic cell death. Mol. Cell. Neurosci. 17:41–53.
Zeron, M.M., Hansson, O., Chen, N., Wellington, C.L., Leavitt, B.R., Brundin, P., Hayden, M.R., and Raymond, L.A. (2002). Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington’s disease [see comment]. Neuron 33:849–860.
Zheng, Y., Wong, M.L., Alberts, B., and Mitchison, T. (1998). Purification and assay of gamma tubulin ring complex. Methods Enzymol. 298:218–228.
Zhou, H., Cao, F., Wang, Z., Yu, Z.X., Nguyen, H.P., Evans, J., Li, S.H., and Li, X.J. (2003). Huntingtin forms toxic NH2-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity. J. Cell Biol. 163:109–118.
Zwickl, P., Seemuller, E., Kapelari, B., and Baumeister, W. (2001). The proteasome: a supramolecular assembly designed for controlled proteolysis. Adv. Protein Chem. 59:187–222.
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Johnston, J.A. (2006). The Aggresome: Proteasomes, Inclusion Bodies, and Protein Aggregation. In: Uversky, V.N., Fink, A.L. (eds) Protein Misfolding, Aggregation, and Conformational Diseases. Protein Reviews, vol 4. Springer, Boston, MA. https://doi.org/10.1007/0-387-25919-8_10
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