Protein aggregation and degradation mechanisms in neurodegenerative diseases

American Journal of Neurodegenerative Diseases

Volumn 2, Issue 1, 2013, Pages 1-14

  Takalo, Mari ^a   Salminen, Antero ^a   Soininen, Hilkka ^a   Hiltunen, Mikko ^a   Haapasalo, Annakaisa ^a  

^a KUOPIO UNIVERSITY HOSPITAL   (Finland)

Author keywords

Aggresome; Autophagy; Inclusion body; IPOD; JUNQ; Neurodegenerative diseases; Protein misfolding; Protein quality control; Ubiquilin 1; Ubiquitin proteasome system

Indexed keywords

ATAXIN 3; CHAPERONE; HISTONE DEACETYLASE 6; PROTEASOME; PROTEIN; SUPEROXIDE DISMUTASE; UBIQUILIN 1; UBIQUITIN; UNCLASSIFIED DRUG;

AGGRESOME; CHAPERONE-MEDIATED AUTOPHAGY; DEGENERATIVE DISEASE; ENVIRONMENTAL FACTOR; GENE MUTATION; GENETIC POLYMORPHISM; HUMAN; JUXTANUCLEAR QUALITY CONTROL; OXIDATIVE STRESS; PATHOGENESIS; PROTEIN AGGREGATION; PROTEIN DEGRADATION; PROTEIN QUALITY; REVIEW; UBIQUITINATION;

EID: 84980052506     PISSN: None     EISSN: 2165591X     Source Type: Journal    
DOI: None     Document Type: Review

References (111)

1. Soto C. Unfolding the role of protein misfolding in neurodegenerative diseases. Nat Rev Neurosci 2003; 4: 49-60.
2. Ross CA and Poirier MA. Protein aggregation and neurodegenerative disease. Nat Med 2004; 10 Suppl: S10-7.
3. Schubert U, Anton LC, Gibbs J, Norbury CC, Yewdell JW, Bennink JR. Rapid degradation of a large fraction of newly synthesized proteins by proteasomes. Nature 2000; 404: 770-774.
4. Hartl FU, Bracher A, Hayer-Hartl M. Molecular chaperones in protein folding and proteostasis. Nature 2011; 475: 324-332.
5. Ciechanover A, Orian A, Schwartz AL. Ubiquitinmediated proteolysis: biological regulation via destruction. Bioessays 2000; 22: 442-451.
6. Dikic I, Wakatsuki S, Walters KJ. Ubiquitinbinding domains-from structures to functions. Nat Rev Mol Cell Biol 2009; 10: 659-671.
7. Kundu M and Thompson CB. Autophagy: basic principles and relevance to disease. Annu Rev Pathol 2008; 3: 427-455.
8. Ihara Y, Morishima-Kawashima M, Nixon R. The ubiquitin-proteasome system and the autophagic-lysosomal system in Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: 10.1101/cshperspect. a006361.
9. Chen B, Retzlaff M, Roos T, Frydman J. Cellular strategies of protein quality control. Cold Spring Harb Perspect Biol 2011; 3: a004374.
10. Cuervo AM, Wong ES, Martinez-Vicente M. Protein degradation, aggregation, and misfolding. Mov Disord 2010; 25 Suppl 1: S49-54.
11. Hol EM and Scheper W. Protein quality control in neurodegeneration: walking the tight rope between health and disease. J Mol Neurosci 2008; 34: 23-33.
12. Mittal S and Ganesh S. Protein quality control mechanisms and neurodegenerative disorders: Checks, balances and deadlocks. Neurosci Res 2010; 68: 159-166.
13. Chiti F and Dobson CM. Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 2006; 75: 333-366.
14. Bolognesi B, Kumita JR, Barros TP, Esbjorner EK, Luheshi LM, Crowther DC, Wilson MR, Dobson CM, Favrin G, Yerbury JJ. ANS binding reveals common features of cytotoxic amyloid species. ACS Chem Biol 2010; 5: 735-740.
15. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 2003; 300: 486-489.
16. Glenner GG and Wong CW. Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984; 120: 885-890.
17. Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM. Microtubule-associated protein tau. A component of Alzheimer paired helical filaments. J Biol Chem 1986; 261: 6084-6089.
18. Goedert M, Ghetti B, Spillantini MG. Frontotemporal dementia: implications for understanding Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: a006254.
19. Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M. Alpha-synuclein in Lewy bodies. Nature 1997; 388: 839-840.
20. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997; 277: 1990-1993.
21. Bruijn LI, Houseweart MK, Kato S, Anderson KL, Anderson SD, Ohama E, Reaume AG, Scott RW, Cleveland DW. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 1998; 281: 1851-1854.
22. Voisine C, Pedersen JS, Morimoto RI. Chaperone networks: tipping the balance in protein folding diseases. Neurobiol Dis 2010; 40: 12-20.
23. Walker LC and Levine H 3rd. Corruption and spread of pathogenic proteins in neurodegenerative diseases. J Biol Chem 2012; 287: 33109-33115.
24. Balch WE, Morimoto RI, Dillin A, Kelly JW. Adapting proteostasis for disease intervention. Science 2008; 319: 916-919.
25. Haigis MC and Yankner BA. The aging stress response. Mol Cell 2010; 40: 333-344.
26. McNaught KS and Jenner P. Proteasomal function is impaired in substantia nigra in Parkinson's disease. Neurosci Lett 2001; 297: 191-194.
27. Keller JN, Hanni KB, Markesbery WR. Impaired proteasome function in Alzheimer's disease. J Neurochem 2000; 75: 436-439.
28. Keller JN, Hanni KB, Markesbery WR. Possible involvement of proteasome inhibition in aging: implications for oxidative stress. Mech Ageing Dev 2000; 113: 61-70.
29. Cataldo AM, Hamilton DJ, Barnett JL, Paskevich PA, Nixon RA. Abnormalities of the endosomal-lysosomal system in Alzheimer's disease: relationship to disease pathogenesis. Adv Exp Med Biol 1996; 389: 271-280.
30. Kegel KB, Kim M, Sapp E, McIntyre C, Castano JG, Aronin N, DiFiglia M. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci 2000; 20: 7268-7278.
31. Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP, Marquez J, Mouatt-Prigent A, Ruberg M, Hirsch EC, Agid Y. Apoptosis and autophagy in nigral neurons of patients with Parkinson's disease. Histol Histopathol 1997; 12: 25-31.
32. Tarawneh R and Galvin JE. Potential future neuroprotective therapies for neurodegenerative disorders and stroke. Clin Geriatr Med 2010; 26: 125-147.
33. Zigman WB and Lott IT. Alzheimer's disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev 2007; 13: 237-246.
34. Zigman WB, Schupf N, Sersen E, Silverman W. Prevalence of dementia in adults with and without Down syndrome. Am J Ment Retard 1996; 100: 403-412.
35. Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, Gwinn-Hardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science 2003; 302: 841.
36. Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science 1997; 276: 2045-2047.
37. Liscic RM and Breljak D. Molecular basis of amyotrophic lateral sclerosis. Prog Neuropsychopharmacol Biol Psychiatry 2011; 35: 370-372.
38. Tanzi RE. The genetics of Alzheimer disease. Cold Spring Harb Perspect Med 2012; 2: 10.1101/cshperspect. a006296.
39. Dawson TM and Dawson VL. Rare genetic mutations shed light on the pathogenesis of Parkinson disease. J Clin Invest 2003; 111: 145-151.
40. Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science 2004; 304: 1158-1160.
41. Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 1998; 392: 605-608.
42. Singleton A, Myers A, Hardy J. The law of mass action applied to neurodegenerative disease: a hypothesis concerning the etiology and pathogenesis of complex diseases. Hum Mol Genet 2004; 13 Spec No 1: R123-6.
43. Smith MA, Richey Harris PL, Sayre LM, Beckman JS, Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J Neurosci 1997; 17: 2653-2657.
44. Castegna A, Thongboonkerd V, Klein JB, Lynn B, Markesbery WR, Butterfield DA. Proteomic identification of nitrated proteins in Alzheimer's disease brain. J Neurochem 2003; 85: 1394-1401.
45. Sultana R, Perluigi M, Butterfield DA. Protein oxidation and lipid peroxidation in brain of subjects with Alzheimer's disease: insights into mechanism of neurodegeneration from redox proteomics. Antioxid Redox Signal 2006; 8: 2021-2037.
46. Mandelkow EM and Mandelkow E. Biochemistry and cell biology of tau protein in neurofibrillary degeneration. Cold Spring Harb Perspect Med 2012; 2: a006247.
47. Braak E, Braak H, Mandelkow EM. A sequence of cytoskeleton changes related to the formation of neurofibrillary tangles and neuropil threads. Acta Neuropathol 1994; 87: 554-567.
48. Zempel H, Thies E, Mandelkow E, Mandelkow EM. Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci 2010; 30: 11938-11950.
49. Haass C, Kaether C, Thinakaran G, Sisodia S. Trafficking and proteolytic processing of APP. Cold Spring Harb Perspect Med 2012; 2: a006270.
50. Tanzi RE and Bertram L. Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell 2005; 120: 545-555.
51. Hershko A and Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998; 67: 425-479.
52. Navon A and Ciechanover A. The 26 S proteasome: from basic mechanisms to drug targeting. J Biol Chem 2009; 284: 33713-33718.
53. Tan JM, Wong ES, Kirkpatrick DS, Pletnikova O, Ko HS, Tay SP, Ho MW, Troncoso J, Gygi SP, Lee MK, Dawson VL, Dawson TM, Lim KL. Lysine 63-linked ubiquitination promotes the formation and autophagic clearance of protein inclusions associated with neurodegenerative diseases. Hum Mol Genet 2008; 17: 431-439.
54. Long J, Gallagher TR, Cavey JR, Sheppard PW, Ralston SH, Layfield R, Searle MS. Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch. J Biol Chem 2008; 283: 5427-5440.
55. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007; 282: 24131-24145.
56. Knaevelsrud H and Simonsen A. Fighting disease by selective autophagy of aggregateprone proteins. FEBS Lett 2010; 584: 2635-2645.
57. Kopito RR. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol 2000; 10: 524-530.
58. Johnston JA, Ward CL, Kopito RR. Aggresomes: a cellular response to misfolded proteins. J Cell Biol 1998; 143: 1883-1898.
59. Olzmann JA, Li L, Chin LS. Aggresome formation and neurodegenerative diseases: therapeutic implications. Curr Med Chem 2008; 15: 47-60.
60. Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001; 292: 1552-1555.
61. Kaganovich D, Kopito R, Frydman J. Misfolded proteins partition between two distinct quality control compartments. Nature 2008; 454: 1088-1095.
62. Liu XD, Ko S, Xu Y, Fattah EA, Xiang Q, Jagannath C, Ishii T, Komatsu M, Eissa NT. Transient aggregation of ubiquitinated proteins is a cytosolic unfolded protein response to inflammation and endoplasmic reticulum stress. J Biol Chem 2012; 287: 19687-19698.
63. Taylor JP, Tanaka F, Robitschek J, Sandoval CM, Taye A, Markovic-Plese S, Fischbeck KH. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum Mol Genet 2003; 12: 749-757.
64. Liu B, Larsson L, Caballero A, Hao X, Oling D, Grantham J, Nystrom T. The polarisome is required for segregation and retrograde transport of protein aggregates. Cell 2010; 140: 257-267.
65. Grabbe C and Dikic I. Functional roles of ubiquitin-like domain (ULD) and ubiquitin-binding domain (UBD) containing proteins. Chem Rev 2009; 109: 1481-1494.
66. Su V and Lau AF. Ubiquitin-like and ubiquitinassociated domain proteins: significance in proteasomal degradation. Cell Mol Life Sci 2009; 66: 2819-2833.
67. Schlossmacher MG, Frosch MP, Gai WP, Medina M, Sharma N, Forno L, Ochiishi T, Shimura H, Sharon R, Hattori N, Langston JW, Mizuno Y, Hyman BT, Selkoe DJ, Kosik KS. Parkin localizes to the Lewy bodies of Parkinson disease and dementia with Lewy bodies. Am J Pathol 2002; 160: 1655-1667.
68. Maraganore DM, Farrer MJ, Hardy JA, Lincoln SJ, McDonnell SK, Rocca WA. Case-control study of the ubiquitin carboxy-terminal hydrolase L1 gene in Parkinson's disease. Neurology 1999; 53: 1858-1860.
69. Kruger R, Eberhardt O, Riess O, Schulz JB. Parkinson's disease: one biochemical pathway to fit all genes? Trends Mol Med 2002; 8: 236-240.
70. Olzmann JA, Brown K, Wilkinson KD, Rees HD, Huai Q, Ke H, Levey AI, Li L, Chin LS. Familial Parkinson's disease-associated L166P mutation disrupts DJ-1 protein folding and function. J Biol Chem 2004; 279: 8506-8515.
71. Uchihara T, Fujigasaki H, Koyano S, Nakamura A, Yagishita S, Iwabuchi K. Non-expanded polyglutamine proteins in intranuclear inclusions of hereditary ataxias--triple-labeling immunofluorescence study. Acta Neuropathol 2001; 102: 149-152.
72. Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I. CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 1994; 8: 221-228.
73. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003; 115: 727-738.
74. Miki Y, Mori F, Tanji K, Kakita A, Takahashi H, Wakabayashi K. Accumulation of histone deacetylase 6, an aggresome-related protein, is specific to Lewy bodies and glial cytoplasmic inclusions. Neuropathology 2011; 31: 561-568.
75. Lee JY, Koga H, Kawaguchi Y, Tang W, Wong E, Gao YS, Pandey UB, Kaushik S, Tresse E, Lu J, Taylor JP, Cuervo AM, Yao TP. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 2010; 29: 969-980.
76. Olzmann JA, Li L, Chudaev MV, Chen J, Perez FA, Palmiter RD, Chin LS. Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6. J Cell Biol 2007; 178: 1025-1038.
77. Lamark T, Kirkin V, Dikic I, Johansen T. NBR1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell Cycle 2009; 8: 1986-1990.
78. Johansen T and Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011; 7: 279-296.
79. Shin J. P62 and the sequestosome, a novel mechanism for protein metabolism. Arch Pharm Res 1998; 21: 629-633.
80. Vadlamudi RK, Joung I, Strominger JL, Shin J. p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins. J Biol Chem 1996; 271: 20235-20237.
81. Kuusisto E, Salminen A, Alafuzoff I. Ubiquitinbinding protein p62 is present in neuronal and glial inclusions in human tauopathies and synucleinopathies. Neuroreport 2001; 12: 2085-2090.
82. Kuusisto E, Salminen A, Alafuzoff I. Early accumulation of p62 in neurofibrillary tangles in Alzheimer's disease: possible role in tangle formation. Neuropathol Appl Neurobiol 2002; 28: 228-237.
83. Pikkarainen M, Hartikainen P, Alafuzoff I. Neuropathologic features of frontotemporal lobar degeneration with ubiquitin-positive inclusions visualized with ubiquitin-binding protein p62 immunohistochemistry. J Neuropathol Exp Neurol 2008; 67: 280-298.
84. Pikkarainen M, Hartikainen P, Soininen H, Alafuzoff I. Distribution and pattern of pathology in subjects with familial or sporadic late-onset cerebellar ataxia as assessed by p62/sequestosome immunohistochemistry. Cerebellum 2011; 10: 720-731.
85. Salminen A, Kaarniranta K, Haapasalo A, Hiltunen M, Soininen H, Alafuzoff I. Emerging role of p62/sequestosome-1 in the pathogenesis of Alzheimer's disease. Prog Neurobiol 2011; 96: 87-95.
86. Kleijnen MF, Shih AH, Zhou P, Kumar S, Soccio RE, Kedersha NL, Gill G, Howley PM. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell 2000; 6: 409-419.
87. Mah AL, Perry G, Smith MA, Monteiro MJ. Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation. J Cell Biol 2000; 151: 847-862.
88. Ko HS, Uehara T, Tsuruma K, Nomura Y. Ubiquilin interacts with ubiquitylated proteins and proteasome through its ubiquitin-associated and ubiquitin-like domains. FEBS Lett 2004; 566: 110-114.
89. Bertram L, Hiltunen M, Parkinson M, Ingelsson M, Lange C, Ramasamy K, Mullin K, Menon R, Sampson AJ, Hsiao MY, Elliott KJ, Velicelebi G, Moscarillo T, Hyman BT, Wagner SL, Becker KD, Blacker D, Tanzi RE. Family-based association between Alzheimer's disease and variants in UBQLN1. N Engl J Med 2005; 352: 884-894.
90. Hiltunen M, Lu A, Thomas AV, Romano DM, Kim M, Jones PB, Xie Z, Kounnas MZ, Wagner SL, Berezovska O, Hyman BT, Tesco G, Bertram L, Tanzi RE. Ubiquilin 1 modulates amyloid precursor protein trafficking and Abeta secretion. J Biol Chem 2006; 281: 32240-32253.
91. Thomas AV, Herl L, Spoelgen R, Hiltunen M, Jones PB, Tanzi RE, Hyman BT, Berezovska O. Interaction between presenilin 1 and ubiquilin 1 as detected by fluorescence lifetime imaging microscopy and a high-throughput fluorescent plate reader. J Biol Chem 2006; 281: 26400-26407.
92. Deng HX, Chen W, Hong ST, Boycott KM, Gorrie GH, Siddique N, Yang Y, Fecto F, Shi Y, Zhai H, Jiang H, Hirano M, Rampersaud E, Jansen GH, Donkervoort S, Bigio EH, Brooks BR, Ajroud K, Sufit RL, Haines JL, Mugnaini E, Pericak-Vance MA, Siddique T. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 2011; 477: 211-215.
93. Kleijnen MF, Alarcon RM, Howley PM. The ubiquitin-associated domain of hPLIC-2 interacts with the proteasome. Mol Biol Cell 2003; 14: 3868-3875.
94. Lu A, Hiltunen M, Romano DM, Soininen H, Hyman BT, Bertram L, Tanzi RE. Effects of ubiquilin 1 on the unfolded protein response. J Mol Neurosci 2009; 38: 19-30.
95. Haapasalo A, Viswanathan J, Bertram L, Soininen H, Tanzi RE, Hiltunen M. Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation. Biochem Soc Trans 2010; 38: 150-155.
96. Viswanathan J, Haapasalo A, Bottcher C, Miettinen R, Kurkinen KM, Lu A, Thomas A, Maynard CJ, Romano D, Hyman BT, Berezovska O, Bertram L, Soininen H, Dantuma NP, Tanzi RE, Hiltunen M. Alzheimer's disease-associated ubiquilin-1 regulates presenilin-1 accumulation and aggresome formation. Traffic 2011; 12: 330-348.
97. Haapasalo A, Viswanathan J, Kurkinen KM, Bertram L, Soininen H, Dantuma NP, Tanzi RE, Hiltunen M. Involvement of ubiquilin-1 transcript variants in protein degradation and accumulation. Commun Integr Biol 2011; 4: 428-432.
98. N'Diaye EN, Kajihara KK, Hsieh I, Morisaki H, Debnath J, Brown EJ. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO Rep 2009; 10: 173-179.
99. Rothenberg C, Srinivasan D, Mah L, Kaushik S, Peterhoff CM, Ugolino J, Fang S, Cuervo AM, Nixon RA, Monteiro MJ. Ubiquilin functions in autophagy and is degraded by chaperone-mediated autophagy. Hum Mol Genet 2010; 19: 3219-3232.
100. Wu S, Mikhailov A, Kallo-Hosein H, Hara K, Yonezawa K, Avruch J. Characterization of ubiquilin 1, an mTOR-interacting protein. Biochim Biophys Acta 2002; 1542: 41-56.
101. Ko HS, Uehara T, Nomura Y. Role of ubiquilin associated with protein-disulfide isomerase in the endoplasmic reticulum in stress-induced apoptotic cell death. J Biol Chem 2002; 277: 35386-35392.
102. Lim PJ, Danner R, Liang J, Doong H, Harman C, Srinivasan D, Rothenberg C, Wang H, Ye Y, Fang S, Monteiro MJ. Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD. J Cell Biol 2009; 187: 201-217.
103. Wang S and Kaufman RJ. The impact of the unfolded protein response on human disease. J Cell Biol 2012; 197: 857-867.
104. Massey LK, Mah AL, Ford DL, Miller J, Liang J, Doong H, Monteiro MJ. Overexpression of ubiquilin decreases ubiquitination and degradation of presenilin proteins. J Alzheimers Dis 2004; 6: 79-92.
105. Massey LK, Mah AL, Monteiro MJ. Ubiquilin regulates presenilin endoproteolysis and modulates gamma-secretase components, Pen-2 and nicastrin. Biochem J 2005; 391: 513-525.
106. Heir R, Ablasou C, Dumontier E, Elliott M, Fagotto-Kaufmann C, Bedford FK. The UBL domain of PLIC-1 regulates aggresome formation. EMBO Rep 2006; 7: 1252-1258.
107. Doi H, Mitsui K, Kurosawa M, Machida Y, Kuroiwa Y, Nukina N. Identification of ubiquitininteracting proteins in purified polyglutamine aggregates. FEBS Lett 2004; 571: 171-176.
108. Wang H, Lim PJ, Yin C, Rieckher M, Vogel BE, Monteiro MJ. Suppression of polyglutamine-induced toxicity in cell and animal models of Huntington's disease by ubiquilin. Hum Mol Genet 2006; 15: 1025-1041.
109. Wang H and Monteiro MJ. Ubiquilin interacts and enhances the degradation of expandedpolyglutamine proteins. Biochem Biophys Res Commun 2007; 360: 423-427.
110. Kim SH, Shi Y, Hanson KA, Williams LM, Sakasai R, Bowler MJ, Tibbetts RS. Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1. J Biol Chem 2009; 284: 8083-8092.
111. Hanson KA, Kim SH, Wassarman DA, Tibbetts RS. Ubiquilin modifies TDP-43 toxicity in a Drosophila model of amyotrophic lateral sclerosis (ALS). J Biol Chem 2010; 285: 11068-11072.