Huntingtin forms toxic NH2-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity

Journal of Cell Biology

Volumn 163, Issue 1, 2003, Pages 109-118

  Zhou, Hui ^a   Cao, Fengli ^a   Wang, Zhishan ^a   Yu, Zhao Xue ^a   Nguyen, Huu Phuc ^a   Evans, Joy ^a   Li, Shi Hua ^a   Li, Xiao Jiang ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Aggregates; Aging; Huntington's disease; Polyglutamine; Proteolysis

Indexed keywords

HUNTINGTIN;

AGE DISTRIBUTION; AMINO TERMINAL SEQUENCE; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELL NUCLEUS INCLUSION BODY; COMPLEX FORMATION; CONTROLLED STUDY; DRUG EFFICACY; ENZYME ACTIVITY; GENE MUTATION; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; INHIBITION KINETICS; MOUSE; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN BINDING; SYMPTOMATOLOGY; TOXICITY TESTING;

ANIMALS; ANTIBODIES; BRAIN; CYSTEINE ENDOPEPTIDASES; HUMANS; HUNTINGTON DISEASE; MICE; MULTIENZYME COMPLEXES; MUTATION; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; PEPTIDES; PROTEASOME ENDOPEPTIDASE COMPLEX;

ANIMALIA;

EID: 0141891952     PISSN: 00219525     EISSN: None     Source Type: Journal    
DOI: 10.1083/jcb.200306038     Document Type: Article

References (42)

1. Beal, M.F., E. Brouillet, B.G. Jenkins, R.J. Ferrante, N.W. Kowall, J.M. Miller, E. Storey, R. Srivastava, B.R. Rosen, and B.T. Hyman. 1993. Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 13:4181-4192.
2. Bence, N.F., R.M. Sampat, and R.R. Kopito. 2001. Impairment of the ubiquitin-proteasome system by protein aggregation. Science. 292:1552-1555.
3. Bulteau, A.L., I. Petropoulos, and B. Friguet. 2000. Age-related alterations of proteasome structure and function in aging epidermis. Exp. Gerontol. 35:767-777.
4. Canu, N., C. Barbato, M.T. Ciotti, A. Serafino, L. Dus, and P. Calissano. 2000. Proteasome involvement and accumulation of ubiquitinated proteins in cerebellar granule neurons undergoing apoptosis. J. Neurosci. 20:589-599.
5. Cooper, J.K., G. Schilling, M.F. Peters, W.J. Herring, A.H. Sharp, Z. Kaminsky, J. Masone, F.A. Khan, M. Delanoy, D.R. Borchelt, et al. 1998. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum. Mol. Genet. 7:783-790.
6. Coux, O., K. Tanaka, and A.L. Goldberg. 1996. Structure and functions of the 20S and 26S proteasomes. Annu. Rev. Biochem. 65:801-847.
7. Dardevet, D., C. Sornet, D. Taillandier, I. Savary, D. Attaix, and J. Grizard. 1995. Sensitivity and protein turnover response to glucocorticoids are different in skeletal muscle from adult and old rats. Lack of regulation of the ubiquitin-proteasome proteolytic pathway in aging. J. Clin. Invest. 96:2113-2119.
8. Davies, S.W., M. Turmaine, B.A. Cozens, M. DiFiglia, A.H. Sharp, C.A. Ross, E. Scherzinger, E.E. Wanker, L. Mangiarini, and G.P. Bares. 1997. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. 90:537-548.
9. DiFiglia, M., E. Sapp, K.O. Chase, S.W. Davies, G.P. Bates, J.P. Vonsattel, and N. Aronin. 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 277:1990-1993.
10. Dyer, R.B., and C.T. McMurray. 2001. Mutant protein in Huntington disease is resistant to proteolysis in affected brain. Nat. Genet. 29:270-278.
11. Esler, W.P., and M.S. Wolfe. 2001. A portrait of Alzheimer secretases-new features and familiar faces. Science. 293:1449-1454.
12. Figueiredo-Pereira, M.E., K.A. Berg, and S. Wilk. 1994. A new inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (20S proteasome) induces accumulation of ubiquitin-protein conjugates in a neuronal cell. J. Neurochem. 63:1578-1581.
13. Gafni, J., and L.M. Ellerby. 2002. Calpain activation in Huntington's disease. J. Neurosci. 22:4842-4849.
14. Goffredo, D., D. Rigamonti, M. Tartari, A. De Micheli, C. Verderio, M. Matteoli, C. Zuccato, and E. Cattaneo. 2002. Calcium-dependent cleavage of endogenous wild-type huntingtin in primary cortical neurons. J. Biol. Chem. 277:39594-39598.
15. Gutekunst, C.A., S.H. Li, H. Yi, J.S. Multoy, S. Kuemmerle, R. Jones, D. Rye, R.J. Ferrante, S.M. Hersch, and X.J. Li. 1999. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. 19:2522-2534.
16. Hackam, A.S., R. Singaraja, C.L. Wellington, M. Metzler, K. McCutcheon, T. Zhang, M. Kalchman, and M.R. Hayden. 1998. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J. Cell Biol. 141:1097-1105.
17. Hazeki, N., T. Tsukamoto, I. Yazawa, M. Koyama, S. Hattori, I. Someki, T. Iwatsubo, K. Nakamura, J. Goto, and I. Kanazawa. 2002. Ultrastructure of nuclear aggregates formed by expressing an expanded polyglutamine. Biochem. Biophys. Res. Commun. 294:429-440.
18. Johnston, J.A., C.L. Ward, and R.R. Kopito. 1998. Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143:1883-1898.
19. Keller, J.N., F.F. Huang, and W.R. Markesbery. 2000. Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience. 98:149-156.
20. Kim, Y.J., Y. Yi, E. Sapp, Y. Wang, B. Cuiffo, K.B. Kegel, Z.H. Qin, N. Aronin, and M. DiFiglia. 2001. Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington's disease brains, associate with membranes, and undergo calpain-dependent proteolysis. Proc. Natl. Acad. Sci. USA. 98:12784-12789.
21. Lee, D.H., and A.L. Goldberg. 1998. Proteasome inhibitors: valuable new tools for cell biologists. Trends Cell Biol. 8:397-403.
22. Lee, C.K., R. Weindruch, and T.A. Prolla. 2000. Gene-expression profile of the ageing brain in mice. Nat. Genet. 25:294-297.
23. Li, H., S.H. Li, H. Johnston, P.F. Shelbourne, and X.J. Li. 2000. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet. 25:385-389.
24. Li, S.H., A.L. Cheng, H. Li, and X.J. Li. 1999. Cellular defects and altered gene expression in PC12 cells stably expressing mutant huntingtin. J. Neurosci. 19:5159-5172.
25. Li, S.H., A.L. Cheng, H. Zhou, S. Lam, M. Rao, H. Li, and X.J. Li. 2002. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol. Cell. Biol. 22:1277-1287.
26. Lin, C.H., S. Tallaksen-Greene, W.M. Chien, J.A. Cearley, W.S. Jackson, A.B. Crouse, S. Ren, X.J. Li, R.L. Albin, and P.J. Detloff. 2001. Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum. Mol. Genet. 10:137-144.
27. Lunkes, A., K.S. Lindenberg, L. Ben-Haiem, C. Weber, D. Devys, G.B. Landwehrmeyer, J.L. Mandei, and Y. Trottier. 2002. Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol. Cell. 10:259-269.
28. Martin-Aparicio, E., A. Yamamoto, F. Hernandez, R. Hen, J. Avila, and J.J. Lucas. 2001. Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J. Neurosci. 21:8772-8781.
29. Mende-Mueller, L.M., T. Toneff, S.R. Hwang, M.F. Chesselet, and V.Y. Hook. 2001. Tissue-specific proteolysis of Huntingtin (htt) in human brain: evidence of enhanced levels of N- and C-terminal htt fragments in Huntington's disease striatum. J. Neurosci. 21:1830-1837.
30. Orr, H.T. 2001. Beyond the Qs in the polyglutamine diseases. Genes Dev. 15:925-932.
31. Petropoulos, I., M. Conconi, X. Wang, B. Hoenel, F. Bregegere, Y. Milner, and B. Friguet. 2000. Increase of oxidatively modified protein is associated with a decrease of proteasome activity and content in aging epidermal cells. J. Gerontol. A Biol. Sci. Med. Sci. 55:B220-B227.
32. Piccinini, M., O. Tazartes, M. Mostert, A. Musso, M. DeMarchi, and M.T. Rinaudo. 2000. Structural and functional characterization of 20S and 26S proteasomes from bovine brain. Brain Res. Mol. Brain Res. 76:103-114.
33. Sanchez, I., C. Mahlke, and J. Yuan. 2003. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature. 421:373-379.
34. Schilling, G., M.W. Becher, A.H. Sharp, H.A. Jinnah, K. Duan, J.A. Kotzuk, H.H. Slunt, T. Ratovitski, J.K. Cooper, N.A. Jenkins, et al. 1999. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 8:397-407.
35. Starke-Reed, P.E., and C.N. Oliver. 1989. Protein oxidation and proteolysis during aging and oxidative stress. Arch. Biochem. Biophys. 275:559-567.
36. Sun, B., W. Fan, A. Balciunas, J.K. Cooper, G. Bitan, S. Steavenson, P.E. Denis, Y. Young, B. Adler, L. Daugherty, et al. 2002. Polyglutamine repeat length-dependent proteolysis of huntingtin. Neurobiol. Dis. 11:111-122.
37. Vonsattel, J.P., R.H. Myers, T.J. Stevens, R.J. Ferrante, E.D. Bird, and E.P. Richardson, Jr. 1985. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 44:559-577.
38. Waelter, S., A. Boeddrich, R. Lurz, E. Scherzinger, G. Lueder, H. Lehrach, and E.E. Wanker. 2001. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell. 12:1393-1407.
39. Watase, K., E.J. Weeber, B. Xu, B. Antalffy, L. Yuva-Paylor, K. Hashimoto, M. Kano, R. Atkinson, Y. Sun, D.L. Armstrong, et al. 2002. Along CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron. 34:905-919.
40. Wellington, C.L., L.M. Ellerby, C.A. Gutekunst, D. Rogers, S. Warby, R.K. Graham, O. Loubser, J. van Raamsdonk, R. Singaraja, Y.Z. Yang, et al. 2002. Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J. Neurosci. 22:7862-7872.
41. Wessel, D., and U.I. Flugge. 1984. A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. Anal. Biochem. 138:141-143.
42. Wheeler, V.C., J.K. White, C.A. Gutekunst, V. Vrbanac, M. Weaver, X.J. Li, S.H. Li, H. Yi, J.P. Vonsattel, J.F. Gusella, et al. 2000. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 9:503-513.