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The Androgen Receptor and Spinal and Bulbar Muscular Atrophy

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Zinc Finger Proteins

Part of the book series: Molecular Biology Intelligence Unit ((MBIU))

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Abstract

The androgen receptor belongs to the superfamily of nuclear receptors, which are ligand-dependent transcription factors. In the absence of the androgen, the receptor is localized to the cytoplasm where it is associated with heat shock proteins. Upon ligand binding, the receptor translocates into the nucleus and interacts with specific DNA sequences, called androgen response elements. The DNA-bound receptor interacts with the transcription initiation complex to regulate transcription.

The structural organization of the androgen receptor is very similar to the other members of the steroid receptor family, with an N-terminal transcriptional regulatory domain, a centrally positioned C2C2 zinc finger DNA binding domain, and a C-terminal ligand binding domain. The N-terminal domain contains a polymorphic polyglutamine tract encoded by a trinucleotide (CAG) repeat; the polyglutamine tract normally consists of 9–36 glutamines. Pathological expansion of the androgen receptor polyglutamine tract to 40–62 glutamines causes spinal and bulbar muscular atrophy, a slowly progressive, X-linked motor neuron disease.

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References

  1. Zhou ZX, Wong CI, Sar M et al. The androgen receptor: An overview. Recent Prog Horm Res 1994; 49:249–274.

    PubMed  CAS  Google Scholar 

  2. Wilson EM, French FS. Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. J Biol Chem 1976; 251:5620–5629.

    PubMed  CAS  Google Scholar 

  3. Wilbert DM, Griffin JE, Wilson JD. Characterization of the cytosol androgen receptor of the human prostate. J Clin Endocrinol Metab 1983; 56:113–120.

    PubMed  CAS  Google Scholar 

  4. Zhou ZX, Lane MV, Kemppainen JA et al. Specificity of ligand-dependent androgen receptor stabilization: Receptor domain interactions influence ligand dissociation and receptor stability. Mol Endocrinol 1995; 9:208–218.

    PubMed  CAS  Google Scholar 

  5. Brinkmann AO. Molecular basis of androgen insensitivity. Mol Cell Endocrinol 2001; 179:105–109.

    PubMed  CAS  Google Scholar 

  6. Brinkmann AO, Trapman J. Androgen receptor mutants that affect normal growth and development. Cancer Surv 1992; 14:95–111.

    PubMed  CAS  Google Scholar 

  7. MacLean HE, Warne GL, Zajac JD. Localization of functional domains in the androgen receptor. J Steroid Biochem Mol Biol 1997; 62:233–242.

    PubMed  CAS  Google Scholar 

  8. Pratt WB, Welsh MJ. Chaperone functions of the heat shock proteins associated with steroid receptors. Semin Cell Biol 1994; 5:83–93.

    PubMed  CAS  Google Scholar 

  9. Smith DF, Toft DO. Steroid receptors and their associated proteins. Mol Endocrinol 1993; 7:4–11.

    PubMed  CAS  Google Scholar 

  10. Veldscholte J, Berrevoets CA, Zegers ND et al. Hormone-induced dissociation of the androgen receptor-heat-shock protein complex: Use of a new monoclonal antibody to distinguish transformed from nontransformed receptors. Biochemistry 1992; 31:7422–7430.

    PubMed  CAS  Google Scholar 

  11. Moudgil VK. Phosphorylation of steroid hormone receptors. Biochim Biophys Acta 1990; 1055:243–258.

    PubMed  CAS  Google Scholar 

  12. Brinkmann AO, Blok LJ, de Ruiter PE et al. Mechanisms of androgen receptor activation and function. J Steroid Biochem Mol Biol 1999; 69:307–313.

    PubMed  CAS  Google Scholar 

  13. Jenster G, de Ruiter PE, van der Korput HA et al. Changes in the abundance of androgen receptor isotypes: Effects of ligand treatment, glutamine-stretch variation, and mutation of putative phosphorylation sites. Biochemistry 1994; 33:14064–14072.

    PubMed  CAS  Google Scholar 

  14. Fu M, Wang C, Reutens AT et al. p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. J Biol Chem 2000; 275:20853–20860.

    PubMed  CAS  Google Scholar 

  15. Lieberman AP, Harmison G, Strand AD et al. Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor. Hum Mol Genet 2002; 11:1967–1976.

    PubMed  CAS  Google Scholar 

  16. Poukka H, Karvonen U, Janne OA et al. Covalent modification of the androgen receptor by small ubiquitin-like modifier 1 (SUMO-1). Proc Natl Acad Sci USA 2000; 97:14145–14150.

    PubMed  CAS  Google Scholar 

  17. Kuil CW, Berrevoets CA, Mulder E. Ligand-induced conformational alterations of the androgen receptor analyzed by limited trypsinization. Studies on the mechanism of antiandrogen action. J Biol Chem 1995; 270:27569–27576.

    PubMed  CAS  Google Scholar 

  18. Lee DK, Duan HO, Chang C. From androgen receptor to the general transcription factor TFIIH. Identification of cdk activating kinase (CAK) as an androgen receptor NH(2)-terminal associated coactivator. J Biol Chem 2000; 275:9308–9313.

    PubMed  CAS  Google Scholar 

  19. McKenna NJ, Lanz RB, O’Malley BW. Nuclear receptor coregulators: Cellular and molecular biology. Endocr Rev 1999; 20:321–344.

    PubMed  CAS  Google Scholar 

  20. Nikolov DB, Burley SK. RNA polymerase II transcription initiation: A structural view. Proc Natl Acad Sci USA 1997; 94:15–22.

    PubMed  CAS  Google Scholar 

  21. Chang CS, Kokontis J, Liao ST. Molecular cloning of human and rat complementary DNA encoding androgen receptors. Science 1988; 240:324–326.

    PubMed  CAS  Google Scholar 

  22. Lubahn DB, Joseph DR, Sullivan PM et al. Cloning of human androgen receptor complementary DNA and localization to the X chromosome. Science 1988; 240:327–330.

    PubMed  CAS  Google Scholar 

  23. Tilley WD, Marcelli M, Wilson JD et al. Characterization and expression of a cDNA encoding the human androgen receptor. Proc Natl Acad Sci USA 1989; 86:327–331.

    PubMed  CAS  Google Scholar 

  24. Matias PM, Donner P, Coelho R et al. Structural evidence for ligand specificity in the binding domain of the human androgen receptor. Implications for pathogenic gene mutations. J Biol Chem 2000; 275:26164–26171.

    PubMed  CAS  Google Scholar 

  25. Sack JS, Kish KF, Wang C et al. Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc Natl Acad Sci USA 2001; 98:4904–4909.

    PubMed  CAS  Google Scholar 

  26. Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: Structure and function. Curr Opin Cell Biol 1998; 10:384–391.

    PubMed  CAS  Google Scholar 

  27. Pratt WB, Toft DO. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev 1997; 18:306–360.

    PubMed  CAS  Google Scholar 

  28. Reynolds PD, Ruan Y, Smith DF et al. Glucocorticoid resistance in the squirrel monkey is associated with overexpression of the immunophilin FKBP51. J Clin Endocrinol Metab 1999; 84:663–669.

    PubMed  CAS  Google Scholar 

  29. Smith DF. Chaperones in progesterone receptor complexes. Semin Cell Dev Biol 2000; 11:45–52.

    PubMed  Google Scholar 

  30. Jenster G, van der Korput HA, van Vroonhoven C et al. Domains of the human androgen receptor involved in steroid binding, transcriptional activation, and subcellular localization. Mol Endocrinol 1991; 5:1396–1404.

    PubMed  CAS  Google Scholar 

  31. Evans RM. The steroid and thyroid hormone receptor superfamily. Science 1988; 240:889–895.

    PubMed  CAS  Google Scholar 

  32. Claessens F, Verrijdt G, Schoenmakers E et al. Selective DNA binding by the androgen receptor as a mechanism for hormone-specific gene regulation. J Steroid Biochem Mol Biol 2001; 76:23–30.

    PubMed  CAS  Google Scholar 

  33. Kasper S, Rennie PS, Bruchovsky N et al. Cooperative binding of androgen receptors to two DNA sequences is required for androgen induction of the probasin gene. J Biol Chem 1994; 269:31763–769.

    PubMed  CAS  Google Scholar 

  34. Schoenmakers E, Alen P, Verrijdt G et al. Differential DNA binding by the androgen and glucocorticoid receptors involves the second Zn-finger and a C-terminal extension of the DNA-binding domains. Biochem J 1999; 341 (Pt 3):515–521.

    PubMed  CAS  Google Scholar 

  35. Beato M. Gene regulation by steroid hormones. Cell 1989; 56:335–344.

    PubMed  CAS  Google Scholar 

  36. Umesono K, Evans RM. Determinants of target gene specificity for steroid/thyroid hormone receptors. Cell 1989; 57:1139–1146.

    PubMed  CAS  Google Scholar 

  37. Zoppi S, Marcelli M, Deslypere JP et al. Amino acid substitutions in the DNA-binding domain of the human androgen receptor are a frequent cause of receptor-binding positive androgen resistance. Mol Endocrinol 1992; 6:409–415.

    PubMed  CAS  Google Scholar 

  38. Quigley CA, De Bellis A, Marschke KB et al. Androgen receptor defects: Historical, clinical, and molecular perspectives. Endocr Rev 1995; 16:271–321.

    PubMed  CAS  Google Scholar 

  39. Lumbroso S, Lobaccaro JM, Belon C et al. A new mutation within the deoxyribonucleic acid-binding domain of the androgen receptor gene in a family with complete androgen insensitivity syndrome. Fertil Steril 1993; 60:814–819.

    PubMed  CAS  Google Scholar 

  40. Tsai MJ, O’Malley BW. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem 1994; 63:451–486.

    PubMed  CAS  Google Scholar 

  41. Kallio PJ, Palvimo JJ, Mehto M et al. Analysis of androgen receptor-DNA interactions with receptor proteins produced in insect cells. J Biol Chem 1994; 269:11514–11522.

    PubMed  CAS  Google Scholar 

  42. Jenster G, Trapman J, Brinkmann AO. Nuclear import of the human androgen receptor. Biochem J 1993; 293 (Pt 3):761–768.

    PubMed  CAS  Google Scholar 

  43. Simental JA, Sar M, Lane MV et al. Transcriptional activation and nuclear targeting signals of the human androgen receptor. J Biol Chem 1991; 266:510–518.

    PubMed  CAS  Google Scholar 

  44. Picard D, Yamamoto KR. Two signals mediate hormone-dependent nuclear localization of the glucocorticoid receptor. EMBO J 1987; 6:3333–3340.

    PubMed  CAS  Google Scholar 

  45. Jenster G, van der Korput HA, Trapman J et al. Identification of two transcription activation units in the N-terminal domain of the human androgen receptor. J Biol Chem 1995; 270:7341–7346.

    PubMed  CAS  Google Scholar 

  46. McEwan IJ, Gustafsson J. Interaction of the human androgen receptor transactivation function with the general transcription factor TFIIF. Proc Natl Acad Sci USA 1997; 94:8485–8490.

    PubMed  CAS  Google Scholar 

  47. Ikonen T, Palvimo JJ, Janne OA. Interaction between the amino-and carboxyl-terminal regions of the rat androgen receptor modulates transcriptional activity and is influenced by nuclear receptor coactivators. J Biol Chem 1997; 272:29821–29828.

    PubMed  CAS  Google Scholar 

  48. He B, Kemppainen JA, Voegel JJ et al. Activation function 2 in the human androgen receptor ligand binding domain mediates interdomain communication with the NH(2)-terminal domain. J Biol Chem 1999; 274:37219–37225.

    PubMed  CAS  Google Scholar 

  49. He B, Wilson EM. The NH(2)-terminal and carboxyl-terminal interaction in the human androgen receptor. Mol Genet Metab 2002; 75:293–298.

    PubMed  CAS  Google Scholar 

  50. Gao T, Marcelli M, McPhaul MJ. Transcriptional activation and transient expression of the human androgen receptor. J Steroid Biochem Mol Biol 1996; 59:9–20.

    PubMed  CAS  Google Scholar 

  51. Liu YZ, Chrivia JC, Latchman DS. Nerve growth factor up-regulates the transcriptional activity of CBP through activation of the p42/p44(MAPK) cascade. J Biol Chem 1998; 273:32400–32407.

    PubMed  CAS  Google Scholar 

  52. Tanese N, Saluja D, Vassallo MF et al. Molecular cloning and analysis of two subunits of the human TFIID complex: hTAFII130 and hTAFII100. Proc Natl Acad Sci USA 1996; 93:13611–13616.

    PubMed  CAS  Google Scholar 

  53. Chamberlain NL, Driver ED, Miesfeld RL. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Res 1994; 22:3181–3186.

    PubMed  CAS  Google Scholar 

  54. Kazemi-Esfarjani P, Trifiro MA, Pinsky L. Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor: Possible pathogenetic relevance for the (CAG)n-expanded neuronopathies. Hum Mol Genet 1995; 4:523–527.

    PubMed  CAS  Google Scholar 

  55. Tut TG, Ghadessy FJ, Trifiro MA et al. Long polyglutamine tracts in the androgen receptor are associated with reduced trans-activation, impaired sperm production, and male infertility. J Clin Endocrinol Metab 1997; 82:3777–3782.

    PubMed  CAS  Google Scholar 

  56. Schoenberg MP, Hakimi JM, Wang SP et al. Microsatellite Mutation (Cag24→18) in the Androgen Receptor Gene in Human Prostate Cancer. Biochemical and Biophysical Research Communications 1994; 198:74–80.

    PubMed  CAS  Google Scholar 

  57. Hsing AW, Gao Y-T, Wu G et al. Polymorphic CAG and GGN Repeat Lengths in the Androgen Receptor Gene and Prostate Cancer Risk: A Population-based Case-Control Study in China. Cancer Res 2000; 60:5111–5116.

    PubMed  CAS  Google Scholar 

  58. Giovannucci E, Stampfer MJ, Krithivas K et al. The CAG repeat within the androgen receptor gene and its relationship to prostate cancer. Proc Natl Acad Sci USA 1997; 94:3320–3323.

    PubMed  CAS  Google Scholar 

  59. La Spada AR, Wilson EM, Lubahn DB et al. Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 1991; 352:77–79.

    PubMed  Google Scholar 

  60. Kennedy WR, Alter M, Sung JH. Progressive proximal spinal and bulbar muscular atrophy of late onset. A sex-linked recessive trait. Neurology 1968; 18:671–680.

    PubMed  CAS  Google Scholar 

  61. Harding AE, Thomas PK, Baraitser M et al. X-linked recessive bulbospinal neuronopathy: A report of ten cases. J Neurol Neurosurg Psychiatry 1982; 45:1012–1019.

    PubMed  CAS  Google Scholar 

  62. Hausmanowa-Petrusewicz I, Borkowska J, Janczewski Z. X-linked adult form of spinal muscular atrophy. J Neurol 1983; 229:175–188.

    PubMed  CAS  Google Scholar 

  63. Sobue G, Hashizume Y, Mukai E et al. X-linked recessive bulbospinal neuronopathy. A clinicopathological study. Brain 1989; 112:209–232.

    PubMed  Google Scholar 

  64. Olney RK, Aminoff MJ, So YT. Clinical and electrodiagnostic features of X-linked recessive bulbospinal neuronopathy. Neurology 1991; 41:823–828.

    PubMed  CAS  Google Scholar 

  65. Suzuki T, Endo K, Igarashi S et al. Isolated bilateral masseter atrophy in X-linked recessive bulbospinal neuronopathy. Neurology 1997; 48:539–540.

    PubMed  CAS  Google Scholar 

  66. Sumner CJ, Fischbeck KH. Jaw drop in Kennedy’s disease. Neurology 2002; 59:1471–1472.

    PubMed  Google Scholar 

  67. Antonini G, Gragnani F, Romaniello A et al. Sensory involvement in spinal-bulbar muscular atrophy (Kennedy’s disease). Muscle Nerve 2000; 23:252–258.

    PubMed  CAS  Google Scholar 

  68. Polo A, Teatini F, D’Anna S et al. Sensory involvement in X-linked spino-bulbar muscular atrophy (Kennedy’s syndrome): An electrophysiological study. J Neurol 1996; 243:388–392.

    PubMed  CAS  Google Scholar 

  69. Arbizu T, Santamaria J, Gomez JM et al. A family with adult spinal and bulbar muscular atrophy, X-linked inheritance and associated testicular failure. J Neurol Sci 1983; 59:371–382.

    PubMed  CAS  Google Scholar 

  70. Nagashima T, Seko K, Hirose K et al. Familial bulbo-spinal muscular atrophy associated with testicular atrophy and sensory neuropathy (Kennedy-Alter-Sung syndrome). Autopsy case report of two brothers. J Neurol Sci 1988; 87:141–152.

    PubMed  CAS  Google Scholar 

  71. Warner CL, Griffin JE, Wilson JD et al. X-linked spinomuscular atrophy: A kindred with associated abnormal androgen receptor binding. Neurology 1992; 42:2181–2184.

    PubMed  CAS  Google Scholar 

  72. Sobue G, Doyu M, Kachi T et al. Subclinical phenotypic expressions in heterozygous females of X-linked recessive bulbospinal neuronopathy. J Neurol Sci 1993; 117:74–78.

    PubMed  CAS  Google Scholar 

  73. Mariotti C, Castellotti B, Pareyson D et al. Phenotypic manifestations associated with CAG-repeat expansion in the androgen receptor gene in male patients and heterozygous females: A clinical and molecular study of 30 families. Neuromuscul Disord 2000; 10:391–397.

    PubMed  CAS  Google Scholar 

  74. Schmidt BJ, Greenberg CR, Allingham-Hawkins DJ et al. Expression of X-linked bulbospinal muscular atrophy (Kennedy disease) in two homozygous women. Neurology 2002; 59:770–772.

    PubMed  Google Scholar 

  75. Wang Z, Thibodeau SN. A polymerase chain reaction-based test for spinal and bulbar muscular atrophy. Mayo Clin Proc 1996; 71:397–398.

    PubMed  CAS  Google Scholar 

  76. Taylor J, Lieberman A, Fischbeck K. Repeat expansion and neurological diseases. In: Asbury AM, GM McDonald, WI Goadsby, PJ McArthur JC, eds. Diseases of the Nervous System. 3rd ed. Cambridge: Cambridge University Press, 2002.

    Google Scholar 

  77. La Spada AR, Roling DB, Harding AE et al. Meiotic stability and genotype-phenotype correlation of the trinucleotide repeat in X-linked spinal and bulbar muscular atrophy. Nat Genet 1992; 2:301–304.

    PubMed  Google Scholar 

  78. Doyu M, Sobue G, Mukai E et al. Severity of X-linked recessive bulbospinal neuronopathy correlates with size of the tandem CAG repeat in androgen receptor gene. Ann Neurol 1992; 32:707–710.

    PubMed  CAS  Google Scholar 

  79. Igarashi S, Tanno Y, Onodera O et al. Strong correlation between the number of CAG repeats in androgen receptor genes and the clinical onset of features of spinal and bulbar muscular atrophy. Neurology 1992; 42:2300–2302.

    PubMed  CAS  Google Scholar 

  80. Brooks BP, Paulson HL, Merry DE et al. Characterization of an expanded glutamine repeat androgen receptor in a neuronal cell culture system. Neurobiol Dis 1997; 3:313–323.

    PubMed  CAS  Google Scholar 

  81. Mhatre AN, Trifiro MA, Kaufman M et al. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nat Genet 1993; 5:184–188.

    PubMed  CAS  Google Scholar 

  82. Lieberman AP, Harmison G, Strand AD et al. Altered transcriptional regulation in cells expressing the expanded polyglutamine androgen receptor. Hum Mol Genet 2002; 11:1967–1976.

    PubMed  CAS  Google Scholar 

  83. Kazemi-Esfarjani P, Benzer S. Genetic Suppression of Polyglutamine Toxicity in Drosophila. Science 2000; 287:1837–1840.

    PubMed  CAS  Google Scholar 

  84. Ordway JM, Tallaksen-Greene S, Gutekunst CA et al. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 1997; 91:753–763.

    PubMed  CAS  Google Scholar 

  85. Takeyama K, Ito S, Yamamoto A et al. Androgen-dependent neurodegeneration by polyglutamine-expanded human androgen receptor in Drosophila. Neuron 2002; 35:855–864.

    PubMed  CAS  Google Scholar 

  86. Katsuno M, Adachi H, Kume A et al. Testosterone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron 2002; 35:843–854.

    PubMed  CAS  Google Scholar 

  87. Davies SW, Beardsall K, Turmaine M et al. Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions? Lancet 1998; 351:131–133.

    PubMed  CAS  Google Scholar 

  88. Li M, Miwa S, Kobayashi Y et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol 1998; 44:249–254.

    PubMed  CAS  Google Scholar 

  89. Ellerby LM, Hackam AS, Propp SS et al. Kennedy’s disease: Caspase cleavage of the androgen receptor is a crucial event in cytotoxicity. J Neurochem 1999; 72:185–195.

    PubMed  CAS  Google Scholar 

  90. Scherzinger E, Lurz R, Turmaine M et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 1997; 90:549–558.

    PubMed  CAS  Google Scholar 

  91. Scherzinger E, Sittler A, Schweiger K et al. Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington’s disease pathology. Proc Natl Acad Sci USA 1999; 96:4604–4609.

    PubMed  CAS  Google Scholar 

  92. Perutz MF, Johnson T, Suzuki M et al. Glutamine repeats as polar zippers: Their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci USA 1994; 91:5355–5358.

    PubMed  CAS  Google Scholar 

  93. Perutz MF, Pope BJ, Owen D et al. Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid beta-peptide of amyloid plaques. Proc Natl Acad Sci USA 2002; 99:5596–5600.

    PubMed  CAS  Google Scholar 

  94. Taylor JP, Tanaka F, Robitschek J et al. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum Mol Genet 2003; 12:749–757.

    PubMed  CAS  Google Scholar 

  95. Piccioni F, Pinton P, Simeoni S et al. Androgen receptor with elongated polyglutamine tract forms aggregates that alter axonal trafficking and mitochondrial distribution in motor neuronal processes. Faseb J 2002; 16:1418–1420.

    PubMed  CAS  Google Scholar 

  96. Kobayashi Y, Kume A, Li M et al. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. J Biol Chem 2000; 275:8772–8778.

    PubMed  CAS  Google Scholar 

  97. Bailey CK, Andriola IF, Kampinga HH et al. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy. Hum Mol Genet 2002; 11:515–523.

    PubMed  CAS  Google Scholar 

  98. Adachi H, Katsuno M, Minamiyama M et al. Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. J Neurosci 2003; 23:2203–2211.

    PubMed  CAS  Google Scholar 

  99. McCampbell A, Taylor JP, Taye AA et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet 2000; 9:2197–2202.

    PubMed  CAS  Google Scholar 

  100. Steffan JS, Kazantsev A, Spasic-Boskovic O et al. The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc Natl Acad Sci USA 2000; 97:6763–6768.

    PubMed  CAS  Google Scholar 

  101. Nucifora Jr FC, Sasaki M, Peters MF et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 2001; 291:2423–2428.

    PubMed  CAS  Google Scholar 

  102. McCampbell A, Taye AA, Whitty L et al. Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc Natl Acad Sci USA 2001; 98:15179–15184.

    PubMed  CAS  Google Scholar 

  103. Steffan JS, Bodai L, Pallos J et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001; 413:739–743.

    PubMed  CAS  Google Scholar 

  104. Hockly E, Richon VM, Woodman B et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington’s disease. Proc Natl Acad Sci USA 2003; 100:2041–2046.

    PubMed  CAS  Google Scholar 

  105. Katsuno M, Adachi H, Doyu M, et al. Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat Med 2003; 9:768–73.

    PubMed  CAS  Google Scholar 

  106. Piccioni F, Taylor J, Fischbeck K. Screen for compounds that inhibit polyglutamine-induced Caspase-3 activation. (abstract) Neurology 2003; 60(Suppl 1):A529.

    Google Scholar 

  107. Heemskerk J, Tobin AJ, Ravina B. From chemical to drug: Neurodegeneration drug screening and the ethics of clinical trials. Nat Neurosci 2002; 5(Suppl):1027–1029.

    PubMed  CAS  Google Scholar 

  108. Ross CA. Polyglutamine pathogenesis: Emergence of unifying mechanisms for Huntington’s disease and related disorders. Neuron 2002; 35:819–822.

    PubMed  CAS  Google Scholar 

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  1. Neurogenetics Branch National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA

    Federica Piccioni, Charlotte J. Sumner & Kenneth H. Fischbeck

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  1. Federica Piccioni
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  2. Charlotte J. Sumner
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Correspondence to Kenneth H. Fischbeck .

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  1. Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA

    Shiro Iuchi

  2. Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA

    Natalie Kuldell

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Piccioni, F., Sumner, C.J., Fischbeck, K.H. (2005). The Androgen Receptor and Spinal and Bulbar Muscular Atrophy. In: Iuchi, S., Kuldell, N. (eds) Zinc Finger Proteins. Molecular Biology Intelligence Unit. Springer, Boston, MA. https://doi.org/10.1007/0-387-27421-9_31

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