Mutant protein in Huntington disease is resistant to proteolysis in affected brain (original) (raw)

• Goldberg, Y.P. et al. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nature Genet. 13, 442–449 (1996).
  Article CAS Google Scholar
• Wellington, C.L. et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J. Biol. Chem. 273, 9158–9167 (1998).
  Article CAS Google Scholar
• Gutekunst, C.-A. et al. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. 19, 2522–2534 (1999).
  Article CAS Google Scholar
• Li, H., Li, S.H., Johnston, H., Shelbourne, P.F. & Li, X.J. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nature Genet. 25, 385–389 (2000).
  Article CAS Google Scholar
• Ross, C.A. Intranuclear neuronal inclusions: a common pathogenic mechanism for glutamine-repeat neurodegeneration disease? Neuron 19, 1147–1150 (1997).
  Article CAS Google Scholar
• Sisodia, S.S. Nuclear inclusions in glutamine repeat disorders: are they pernicious, coincidental, or beneficial? Cell 95, 1–4 (1998).
  Article CAS Google Scholar
• DiFiglia, M. et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990–1993 (1997).
  Article CAS Google Scholar
• Mende-Mueller, L.M., Toneff, T., Hwang, S.R., Chesselet, M.F. & Hook, V.Y.H. 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 (2001).
  Article CAS Google Scholar
• Cooper, J.K. et al. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum. Mol. Genet. 7, 783–790 (1998).
  Article CAS Google Scholar
• Hackam, A.S. et al. The influence of huntingtin protein size on nuclear localization and toxicity. J. Cell Biol. 141, 1097–1105 (1998).
  Article CAS Google Scholar
• Li, S.-H. & Li, X.-J. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum. Mol. Genet. 7, 777–782 (1998).
  Article CAS Google Scholar
• Lunkes, A. & Mandel, J.L. A cellular model that recapitulates major pathogenic steps of Huntington's disease. Hum. Mol. Genet. 7, 1355–1361 (1998).
  Article CAS Google Scholar
• Martindale, D. et al. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nature Genet. 18, 150–154 (1998).
  Article CAS Google Scholar
• Saudou, F., Finkbeiner, S., Devys, D. & Greenberg, M.E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 95, 55–66 (1998).
  Article CAS Google Scholar
• Hackam, A.S., Singaraja, R., Zhang, T., Gan, L. & Hayden, M.R. In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington's disease. Hum. Mol. Gen. 8, 25–33 (1999).
  Article CAS Google Scholar
• Kim, M. et al. Mutant huntingtin expression in clonal striatal cells: dissociation of inclusion formation and neuronal survival by caspase inhibition. J. Neurosci. 19, 964–973 (1999).
  Article CAS Google Scholar
• Sánchez, I. et al. Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron 22, 623–633 (1999).
  Article Google Scholar
• Davies, S.W. et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90, 537–548 (1997).
  Article CAS Google Scholar
• Schilling, G. et al. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 8, 943–950 (1999).
  Article CAS Google Scholar
• Yamamoto, A., Lucas, J.J. & Hen, R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101, 57–66 (2000).
  Article CAS Google Scholar
• Klement, I.A. et al. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95, 41–53 (1998).
  Article CAS Google Scholar
• Kuemmerle, S. et al. Huntingtin aggregates may not predict neuronal death in Huntington's disease. Ann. Neurol. 46, 842–849 (1999).
  Article CAS Google Scholar
• Wellington, C.L. et al. Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J. Biol. Chem. 275, 19831–19838 (2000).
  Article CAS Google Scholar
• Ona, V.O. et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 399, 264–267 (1999).
  Article Google Scholar
• Mangiarini, L. et al. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87, 493–506 (1996).
  Article CAS Google Scholar
• Scherzinger, E. et al. Huntingtin-encoded polyglutamine expansions form amyloid-like aggregates in vitro and in vivo. Cell 90, 549–558 (1997).
  Article CAS Google Scholar
• Scherzinger, E. et al. 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 (1999).
  Article CAS Google Scholar
• Hazeki, N., Tukamoto, T., Goto, J. & Kanazawa, I. Formic acid dissolves aggregates of an N-terminal huntingtin fragment containing an expanded polyglutamine tract: applying to quantification of protein components of the aggregates. Biochem. Biophys. Res. Commun. 277, 386–393 (2000).
  Article CAS Google Scholar
• Reiner, A. et al. Differential loss of striatal projection neurons in Huntington's disease. Proc. Natl Acad. Sci. USA 85, 5733–5737 (1988).
  Article CAS Google Scholar
• Hedreen, J.C., Peyser, C.E., Folstein, S.E. & Ross, C.A. Neuronal loss in layers V and VI of cerebral cortex in Huntington's disease. Neurosci. Lett. 133, 257–261 (1991).
  Article CAS Google Scholar
• Vonsattel, J.P.G. & DiFiglia, M. Huntington disease. J. Neuropath. Exp. Neurol. 57, 369–384 (1998).
  Article CAS Google Scholar
• Aronin, N. et al. CAG expansion affects the expression of mutant huntingtin in the Huntington's disease brain. Neuron 15, 1193–1201 (1995).
  Article CAS Google Scholar
• Trottier, Y. et al. Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form. Nature Genet. 10, 104–110 (1995).
  Article CAS Google Scholar
• Trottier, Y. et al. Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature 378, 403–406 (1995).
  Article CAS Google Scholar
• Sieradzan, K.A. et al. Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp. Neurol. 156, 92–99 (1999).
  Article CAS Google Scholar
• Becher, M.W. et al. Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol. Dis. 4, 387–397 (1998).
  Article CAS Google Scholar
• Wheeler, V.C. et al. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in _Hdh_Q92 and _Hdh_Q111 knock-in mice. Hum. Mol. Genet. 9, 503–513 (2000).
  Article CAS Google Scholar
• Sharp, A.H. et al. Widespread expression of Huntington's disease gene (IT15) protein product. Neuron 14, 1065–1074 (1995).
  Article CAS Google Scholar
• Steffan, J.S. et al. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl Acad. Sci. USA 97, 6763–6768 (2000).
  Article CAS Google Scholar
• Nucifora Jr, F.C. et al. Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 291, 2423–2428 (2001).
  Article CAS Google Scholar
• Narain, Y., Wyttenbach, A., Rankin, J., Furlong, R.A. & Rubinsztein, D.C. A molecular investigation of true dominance in Huntington's disease. J. Med. Genet. 36, 739–746 (1999).
  Article CAS Google Scholar
• de Cristofaro, T., Affaitati, A., Feliciello, A., Avvedimento, E.V. & Varrone, S. Polyglutamine-mediated aggregation and cell death. Biochem. Biophys. Res. Commun. 272, 818–821 (2000).
  Article Google Scholar
• Huang, C.C. et al. Amyloid formation by mutant huntingtin: threshold, progressivity, and recruitment of normal polyglutamine proteins. Somatic Cell Mol. Genet. 24, 217–233 (1998).
  Article CAS Google Scholar
• Dragatsis, I., Levine, M.S. & Zeitlin, S. Inactivation of Hdh in the brain and testis result in progressive neurodegeneration and sterility in mice. Nature Genet. 26, 300–306 (2000).
  Article CAS Google Scholar
• Goellner, G. et al. Different mechanisms underlie DNA instability in Huntington disease and colorectal cancer. Am. J. Hum. Genet. 60, 879–890 (1997).
  CAS PubMed PubMed Central Google Scholar
• Kovtun, I.V. & McMurray, C.T. Trinucleotide expansion in haploid germ cells by gap repair. Nature Genet. 27, 407–411 (2001).
  Article CAS Google Scholar
• McMurray, C.T., Devi, L., Calavetta, L. & Douglass, J.O. Regulated expression of the prodynorphin gene in the R2C Leydig tumor cell line. Endocrinology 124, 49–59 (1989).
  Article CAS Google Scholar
• Vonsattel, J.P. et al. Neuropathological classification of Huntington's disease. J. Neuropath. Exp. Neurol. 44, 559–577 (1985).
  Article CAS Google Scholar