Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone

Human Molecular Genetics

Volumn 8, Issue 5, 1999, Pages 731-741

  Stenoien, David L ^a   Cummings, Chris J ^b   Adams, Henry P ^a   Mancini, Maureen G ^a   Patel, Kavita ^a   Demartino, George N ^c   Marcelli, Marco ^a   Weigel, Nancy L ^a   Mancini, Michael A ^a  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b MICHAEL E DEBAKEY VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; ANTIBODY; CHAPERONE; GLUTAMINE; HEAT SHOCK PROTEIN 70; HEAT SHOCK PROTEIN 90; PROTEASOME; REGULATOR PROTEIN; STEROID RECEPTOR;

ARTICLE; CELL NUCLEUS; CONTROLLED STUDY; CYTOPLASM; ELECTRON MICROSCOPY; HELA CELL; HUMAN; HUMAN CELL; KENNEDY DISEASE; MITOCHONDRION; PRIORITY JOURNAL;

EID: 0032945938     PISSN: 09646906     EISSN: None     Source Type: Journal    
DOI: 10.1093/hmg/8.5.731     Document Type: Article

References (64)

1. Kennedy, W.R., Alter, M. and Sung, J.H. (1968) Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology, 18, 671-680.
2. Sobue, G., Hashizume, Y., Mukai, E., Hirayama, M., Mitsuma, T. and Takahashi, A. (1989) X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain, 112, 209-232.
3. Fischbeck, K.H., Ionasescu, V., Ritter, A.W., Ionasescu, R., Davies, K., Ball, S., Bosch, P., Burns, T., Hausmanowa-Petrusewicz, I., Borkowska, J., Ringel, S.P. and Stern, L.Z. (1986) Localization of the gene for X-linked spinal muscular atrophy. Neurology, 36, 1595-1598.
4. Brown, C.J., Goss, S.J., Lubahn, D.B., Joseph, D.R., Wilson, E.M., French, F.S. and Willard, H.F. (1989) Androgen receptor locus on the human X chromosome: regional localization to Xq11-12 and description of a DNA polymorphism. Am. J. Hum. Genet., 44, 264-269.
5. Fischbeck, K.H., Souders, D. and La Spada, A. (1991) A candidate gene for X-linked spinal muscular atrophy. Adv. Neurol., 56, 209-213.
6. La Spada, A.R., Wilson, E.M., Lubahn, D.B., Harding, A.E. and Fischbeck, K.H. (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature, 352, 77-79.
7. Orr, H.T., Chung, M.Y., Banfi, S., Kwiatkowski, T.J., Servadio, A., Beaudet, A.L., McCall, A.E., Duvick, L.A., Ranum, L.P. and Zoghbi, H.Y. (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia 1. Nature Genet., 4, 221-226.
8. Kawaguchi, Y., Okamoto, T., Taniwaki, M., Aizawa, M., Inoue, M., Katayama, S., Kawagami, H., Nakamura, S., Nishimura, M., Akiguchi, I. et al. (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nature Genet., 6, 9-13.
9. Imbert, G., Saudou, F., Yvert, G., Devys, D., Trottier, Y., Garnier, J.M., Weber, C., Mandel, J.L., Cancel, G., Abbas, N., Durr, A., Didierjean, O., Stevanin, G., Agid, Y. and Brice, A. (1996) Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nature Genet., 14, 285-291.
10. Becher, M.W., Rubinsztein, D.C., Leggo, J., Wagster, M.V., Stine, O.C., Ranen, N.G., Franz, M.L., Abbott, M.H., Sherr, M., MacMillan, J.C., Barron, L., Porteous, M., Harper, P.S. and Ross, C.A. (1997) Dentatorubral and pallidoluysian atrophy (DRPLA). Clinical and neuropathological findings in genetically confirmed North American and European pedigrees. Mov. Disord., 12, 519-530.
11. David, G., Abbas, N., Stevanin, G., Durr, A., Yvert, G., Cancel, G., Weber, C., Imbert, G., Saudou, F., Antoniou, E., Drabkin, H., Gemmill, R., Giunti, P., Benomar, A., Wood, N., Ruberg, M., Agid, Y., Mandel, J.L. and Brice, A. (1997) Cloning of the SCA7 gene reveals a highly unstable CAG repeat expansion. Nature Genet., 17, 65-70.
12. Zoghbi, H.Y. and Orr, H.T. (1995) Spinocerebellar ataxia type I. Semin. Cell Biol., 6, 29-35.
13. Pulst, S.M., Nechiporuk, A., Nechiporuk, T., Gispert, S., Chen, X.N., Lopes-Cendes, I., Pearlman, S., Starkman, S., Orozco-Diaz, G., Lunkes, A., DeJong, P., Rouleau, G.A., Auburger, G., Korenberg, J.R., Figueroa, C. and Sahba, S. (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinocerebellar ataxia type 2. Nature Genet., 14, 269-276.
14. Skinner, P.J., Koshy, B.T., Cummings, C.J., Klement, I.A., Helin, K., Servadio, A., Zoghbi, H.Y. and Orr, H.T. (1997) Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature, 389, 971-974.
15. Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S.W. and Bates, G.P. (1997) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Nature Genet., 15, 197-200.
16. Davies, S.W., Turmaine, M., Cozens, B.A., DiFiglia, M., Sharp, A.H., Ross, C.A., Scherzinger, E., Wanker, E.E., Mangiarini, L. and Bates, G.P. (1997) Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell, 90, 537-548.
17. DiFiglia, M., Sapp, E., Chase, K.O., Davies, S.W., Bates, G.P., Vonsattel, J.P., Aronin, N. (1997) Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science, 277, 1990-1993.
18. Paulson, H.L., Perez, M.K., Trottier, Y., Trojanowski, J.Q., Subramony, S.H., Das, S.S., Vig, P., Mandel, J.L., Fischbeck, K.H. and Pittman, R.N. (1997) Intranuclear inclusions of expanded polyQ protein in spinocerebellar ataxia type 3. Neuron, 19, 333-344.
19. Li, M., Miwa, S., Kobayashi, Y., Merry, D.E., Yamamoto, M., Tanaka, F., Doyu, M., Hashizume, Y., Fischbeck, K.H. and Sobue, G. (1998) Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann. Neurol., 44, 249-254.
20. Cummings, C.J., Mancini, M.A., Antalffy, B., DeFranco, D.B., Orr, H.T. and Zoghbi, H.Y. (1998) Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nature Genet., 19, 148-154.
21. Tsai, M.J. and O'Malley, B.W. (1994) Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem., 63, 451-486.
22. Shibata, H., Spencer, T.E., Onate, S.A., Jenster, G., Tsai, S.Y., Tsai, M.J. and O'Malley, B.W. (1997) Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action. Rec. Prog. Hormone Res., 52, 141-164.
23. MacLean, H.E., Warne, G.L. and Zajac, J.D. (1997) Localization of functional domains in the androgen receptor. J. Steroid Biochem. Mol. Biol., 62, 233-242.
24. DeFranco, D.B., Ramakrishnan, C. and Tang, Y. (1998) Molecular chaperones and subcellular trafficking of steroid receptors. J. Steroid Biochem. Mol. Biol., 65, 51-58.
25. Pratt, W.B. (1993) The role of heat shock proteins in regulating the function, folding and trafficking of the glucocorticoid receptor. J. Biol. Chem., 268, 21455-21458.
26. Veldscholte, J., Berrevoets, C.A., Zegers, N.D., van der Kwast, T.H., Grootegoed, J.A. and Mulder, E. (1992) Hormone induced dissociation of the androgen receptor-heat shock protein complex: use of a new monoclonal antibody to distinguish transformed and nontransformed receptors. Biochemistry, 31, 7422-7430.
27. Caplan, A.J., Langley, E., Wilson, E.M. and Vidal, J. (1995) Hormone-dependent transactivation by the human androgen receptor is regulated by a dnaJ protein. J. Biol. Chem., 270, 5251-5257.
28. Bohen, S.P., Kralli, A. and Yamamoto, K.R. (1995) Hold 'em and fold 'em: chaperones and signal transduction. Science, 268, 1303-1304.
29. Onate, S.A., Tsai, S.Y., Tsai, M.J. and O'Malley, B.W. (1995) Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science, 270, 1354-1357.
30. Jenster, G., Trapman, J. and Brinkmann, A.O. (1993) Nuclear import of the human androgen receptor. Biochem. J., 293, 761-768.
31. Butler, R., Leigh, P.N., McPhaul, M.J. and Gallo, J.M. (1998) Truncated forms of the androgen receptor are associated with polyQ expansion in X-linked spinal and bulbar muscular atrophy. Hum. Mol. Genet., 7, 121-127.
32. Merry, D.E., Kobayashi, Y., Bailey, C.K., Taye, A.A. and Fischbeck, K.H. (1998) Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy. Hum. Mol. Genet., 7, 693-701.
33. Saudou, F., Finkbeiner, S., Devys, D. and Greenberg, M.E. (1998) Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell, 95, 55-66.
34. Klement, I.A., Skinner, P.J., Kaytor, M.D., Hong, Y., Hersch, S.M., Clark, H.B., Zoghbi, H.Y. and Orr, H.T. (1998) Ataxin-1 nuclear localization and aggregation: role in polyQ-induced disease in SCA1 transgenic mice. Cell, 95, 41-53.
35. Tang, Y., Ramakrishnan, C., Thomas, J. and DeFranco, D.B. (1997) A role for HDJ-2/HSDJ in correcting subnuclear trafficking, transactivation and transrepression defects of a glucocorticoid receptor zinc finger mutant. Mol. Biol. Cell, 8, 795-809.
36. Xiao, N. and DeFranco, D.B. (1997) Overexpression of unliganded steroid receptors activates endogenous heat shock factor. Mol. Endocrinol., 11, 1365-1374.
37. Hendrick, J.P. and Hartl, F.U. (1995) The role of molecular chaperones in protein folding. FASEB J., 9, 1559-1569.
38. Hartl, F.U. (1996) Molecular chaperones in cellular protein folding. Nature, 381, 571-579.
39. Lu, Z. and Cyr, D.M. (1998) The conserved carboxyl terminus and zinc finger-like domain of the co-chaperone Ydj1 assist Hsp70 in protein folding. J. Biol. Chem., 273, 5970-5978.
40. Kumar, S., Yoshida, Y. and Noda, M. (1993) Cloning of a cDNA which encodes a novel ubiquitin-like protein. Biochem. Biophys. Res. Commun., 195, 393-399.
41. Kamitani, T., Kito, K., Nguyen, H.P. and Yeh, E.T. (1997) Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein. J. Biol. Chem., 272, 28557-28562.
42. Nawaz, Z., Lonard, D.M., Smith, C.L., Lev-Lehman, E., Tsai, S.Y., Tsai, M.J. and O'Malley, B.W. (1999) The Angelmar syndrome-associated protein, E6-AP, is a coactivator for the nuclear hormone receptor superfamily. Mol. Cell Biol., 19, 1182-1189.
43. Hershko, A. and Ciechanover, A. (1992) The ubiquitin system for protein degradation. Annu. Rev. Biochem., 61, 761-807.
44. Hochstrasser, M. (1995) Ubiquitin, proteasomes and the regulation of intracellular protein degradation. Curr. Opin. Cell Biol., 7, 215-223.
45. Hochstrasser, M. (1996) Ubiquitin-dependent protein degradation. Annu. Rev. Genet., 30, 405-439.
46. Yoshimura, T., Kameyama, K., Takagi, T., Ikai, A., Tokunaga, F., Koide, T., Tanahashi, N., Tamura, T., Cejka, Z., Baumeister, W., Tanaka, K. and Ichihara, A. (1993) Molecular characterization of the '26S' proteasome complex from rat liver. J. Struct. Biol., 111, 200-211.
47. Peters, J.M. (1994) Proteasomes: protein degradation machines of the cell. Trends Biochem. Sci., 19, 377-382.
48. Coux, O., Tanaka, K. and Goldberg, A.L. (1996) Structure and function of the 20S and 26S proteasomes. Annu. Rev. Biochem., 65, 801-847.
49. Adams, G.M., Falke, S., Goldberg, A.L., Slaughter, C.A., DeMartino, G.N. and Gogol, E.P. (1997) Structural and functional effects of PA700 and modulator protein on proteasomes. J. Mol. Biol., 273, 646-657.
50. Mhatre, A.N., Trifiro, M.A., Kaufman, M., Kazemi-Esfarjani, P., Figlewicz, D., Rouleau, G. and Pinsky, L. (1993) Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nature Genet., 5, 184-188.
51. Jenster, G., de Ruiter, P.E., van der Korput, H.A., Kuiper, G.G., Trapman, J. and Brinkmann, A.O. (1994) Changes in the abundance of androgen receptor isotypes: effects of ligand treatment, glutamine-stretch variation and mutation of putative phosphorylation sites. Biochemistry, 33, 14064-14072.
52. n-expanded neuronopathies. Hum. Mol. Genet., 4, 523-527.
53. Nakajima, H., Kimura, F., Nakagawa, T., Furutama, D., Shinoda, K., Shimizu, A. and Ohsawa, N. (1996) Transcriptional activation by the androgen receptor in X-linked spinal and bulbar muscular atrophy. J. Neurosci., 142, 12-16.
54. Welch, W.J. and Gambetti, P. (1998) Chaperoning brain diseases. Nature, 392, 23-24.
55. DebBurman, S.K., Raymond, G.J., Caughey, B. and Lindquist, S. (1997) Chaperone-supervised conversion of prion protein to its protease-resistant form. Proc. Natl Acad. Sci. USA, 94, 13938-13943.
56. Cyr, D.M., Langer, T. and Douglas, M.G. (1994) DnaJ-like proteins: molecular chaperones and specific regulators of Hsp70. Trends Biochem. Sci., 19, 176-181.
57. DeMartino, G.N., Moomaw, C.R., Zagnitko, O.P., Proske, R.J., Ma, C.P., Afendis, S.J., Swaffield, J.C. and Slaughter, C.A. (1994) PA700, an ATP-dependent activator of the 20S proteasome, is an ATPase containing multiple members of a nucleotide-binding protein family. J. Biol. Chem., 269, 20878-20884.
58. Zajac, J.D. and MacLean, H.E. (1998) Kennedy's disease: clinical aspects. In Wells, R.D. and Warren, S.T. (eds), Genetic Instabilities and Hereditary Neurological Diseases. Academic Press, San Diego, CA, pp. 87-100.
59. Brooks, B.P., Merry, D.E., Paulson, H.L., Lieberman, A.P., Kolson, D.L. and Fischbeck, K.H. (1998) A cell culture model for androgen effects in motor neurons. J. Neurochem., 70, 1054-1060.
60. Tilley, W.D., Marcelli, M., Wilson, J.D. and McPhaul, J.M. (1989) Characterization and cloning of a cDNA encoding the human androgen receptor. Proc. Natl Acad. Sci. USA, 86, 327-331.
61. Gao, T., Marcelli, M. and McPhaul, M. (1996) Transcriptional activation and transient expression of the human androgen receptor. J. Steroid Biochem. Mol. Biol., 59, 9-20.
62. McGuire, M.J., Croall, D.E. and DeMartino, G.N. (1988) ATP-stimulated proteolysis in soluble extracts of BHK 21/C13 cells. Evidence for multiple pathways and a role for an enzyme related to the high-molecular weight protease, macropain. Arch. Biochem. Biophys., 262, 273-285.
63. Ma, C.P., Willy, P.J., Slaughter, C.A. and DeMartino, G.N. (1993) PA28, an activator of the 20S proteasome, is inactivated by proteolytic modification at its carboxyl terminus. J. Biol. Chem., 268, 22514-22519.
64. Agard, D.A. (1984) Optical sectioning microscopy: cellular architecture in three dimensions. Annu. Rev. Biophys. Bioeng., 13, 191-219.