Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (85)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Li, S. H.
Right arrow Articles by Li, X. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, S. H.
Right arrow Articles by Li, X. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol 7, 777-782, Copyright © 1998 by Oxford University Press

ARTICLES

Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats

SH Li and XJ Li
Department of Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.

Huntington's disease (HD) is caused by expansion of a glutamine repeat in huntingtin. Mutant huntingtin contains 36-55 repeats in adult HD patients and >60 repeats in juvenile HD patients. An N-terminal fragment of mutant huntingtin forms aggregates in neuronal nuclei in the brains of transgenic mice and HD patients. Aggregation of expanded polyglutamine is thought to be a common pathological mechanism in HD and other glutamine repeat diseases. It is not clear how the length of the repeats is correlated with formation of protein aggregates. By expressing a series of huntingtin constructs encoding various glutamine repeats (23-150 units) in cultured cells we observed N-terminal fragments of huntingtin (amino acids 1-67 and 1-212), but not full- length huntingtins, with glutamine repeats >/=66 units formed protein aggregates. Huntingtin aggregation was not induced when the repeat was </=49 units and was markedly promoted by very long repeats >/=120 units. This study suggests that various N-terminal fragments of mutant huntingtin can form aggregates and that aggregation is prompted by lengthening the glutamine repeat.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. L. Orr, S. Huang, M. A. Roberts, J. C. Reed, S. Li, and X.-J. Li
Sex-dependent Effect of BAG1 in Ameliorating Motor Deficits of Huntington Disease Transgenic Mice
J. Biol. Chem., June 6, 2008; 283(23): 16027 - 16036.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
J. A. McLear, D. Lebrecht, A. Messer, and W. J. Wolfgang
Combinational approach of intrabody with enhanced Hsp70 expression addresses multiple pathologies in a fly model of Huntington's disease
FASEB J, June 1, 2008; 22(6): 2003 - 2011.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. L. Orr, S. Li, C.-E. Wang, H. Li, J. Wang, J. Rong, X. Xu, P. G. Mastroberardino, J. T. Greenamyre, and X.-J. Li
N-Terminal Mutant Huntingtin Associates with Mitochondria and Impairs Mitochondrial Trafficking
J. Neurosci., March 12, 2008; 28(11): 2783 - 2792.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Fukui and C. T. Moraes
Extended polyglutamine repeats trigger a feedback loop involving the mitochondrial complex III, the proteasome and huntingtin aggregates
Hum. Mol. Genet., April 1, 2007; 16(7): 783 - 797.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. P. Nguyen, P. Kobbe, H. Rahne, T. Worpel, B. Jager, M. Stephan, R. Pabst, C. Holzmann, O. Riess, H. Korr, et al.
Behavioral abnormalities precede neuropathological markers in rats transgenic for Huntington's disease
Hum. Mol. Genet., November 1, 2006; 15(21): 3177 - 3194.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
T. W. Sedlak and S. H. Snyder
Messenger Molecules and Cell Death: Therapeutic Implications
JAMA, January 4, 2006; 295(1): 81 - 89.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
H. Mukai, T. Isagawa, E. Goyama, S. Tanaka, N. F. Bence, A. Tamura, Y. Ono, and R. R. Kopito
Formation of morphologically similar globular aggregates from diverse aggregation-prone proteins in mammalian cells
PNAS, August 2, 2005; 102(31): 10887 - 10892.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
C. M. Everett and N. W. Wood
Trinucleotide repeats and neurodegenerative disease
Brain, November 1, 2004; 127(11): 2385 - 2405.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. G. Hay, K. Sathasivam, S. Tobaben, B. Stahl, M. Marber, R. Mestril, A. Mahal, D. L. Smith, B. Woodman, and G. P. Bates
Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach
Hum. Mol. Genet., July 1, 2004; 13(13): 1389 - 1405.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
T. Okuda, H. Hattori, S. Takeuchi, J. Shimizu, H. Ueda, J. J. Palvimo, I. Kanazawa, H. Kawano, M. Nakagawa, and H. Okazawa
PQBP-1 transgenic mice show a late-onset motor neuron disease-like phenotype
Hum. Mol. Genet., April 1, 2003; 12(7): 711 - 725.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. Dedeoglu, J. K. Kubilus, T. M. Jeitner, S. A. Matson, M. Bogdanov, N. W. Kowall, W. R. Matson, A. J. L. Cooper, R. R. Ratan, M. F. Beal, et al.
Therapeutic Effects of Cystamine in a Murine Model of Huntington's Disease
J. Neurosci., October 15, 2002; 22(20): 8942 - 8950.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. W. Dunah, H. Jeong, A. Griffin, Y.-M. Kim, D. G. Standaert, S. M. Hersch, M. M. Mouradian, A. B. Young, N. Tanese, and D. Krainc
Sp1 and TAFII130 Transcriptional Activity Disrupted in Early Huntington's Disease
Science, June 21, 2002; 296(5576): 2238 - 2243.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Gafni and L. M. Ellerby
Calpain Activation in Huntington's Disease
J. Neurosci., June 15, 2002; 22(12): 4842 - 4849.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J.-Z. Chuang, H. Zhou, M. Zhu, S.-H. Li, X.-J. Li, and C.-H. Sung
Characterization of a Brain-enriched Chaperone, MRJ, That Inhibits Huntingtin Aggregation and Toxicity Independently
J. Biol. Chem., May 24, 2002; 277(22): 19831 - 19838.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Khoshnan, J. Ko, and P. H. Patterson
Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity
PNAS, January 22, 2002; 99(2): 1002 - 1007.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
K. Sathasivam, B. Woodman, A. Mahal, F. Bertaux, E. E. Wanker, D. T. Shima, and G. P. Bates
Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington's disease (HD) transgenic mice and HD patients
Hum. Mol. Genet., October 1, 2001; 10(21): 2425 - 2435.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Petersen, K. E. Larsen, G. G. Behr, N. Romero, S. Przedborski, P. Brundin, and D. Sulzer
Expanded CAG repeats in exon 1 of the Huntington's disease gene stimulate dopamine-mediated striatal neuron autophagy and degeneration
Hum. Mol. Genet., June 1, 2001; 10(12): 1243 - 1254.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
T. B. Freeman, F. Cicchetti, R. A. Hauser, T. W. Deacon, X.-J. Li, S. M. Hersch, G. M. Nauert, P. R. Sanberg, J. H. Kordower, S. Saporta, et al.
Transplanted fetal striatum in Huntington's disease: Phenotypic development and lack of pathology
PNAS, December 5, 2000; 97(25): 13877 - 13882.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
G. Cancel, C. Duyckaerts, M. Holmberg, C. Zander, G. Yvert, A.-S. Lebre, M. Ruberg, B. Faucheux, Y. Agid, E. Hirsch, et al.
Distribution of ataxin-7 in normal human brain and retina
Brain, December 1, 2000; 123(12): 2519 - 2530.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Restituito, R. M. Thompson, J. Eliet, R. S. Raike, M. Riedl, P. Charnet, and C. M. Gomez
The Polyglutamine Expansion in Spinocerebellar Ataxia Type 6 Causes a beta Subunit-Specific Enhanced Activation of P/Q-Type Calcium Channels in Xenopus Oocytes
J. Neurosci., September 1, 2000; 20(17): 6394 - 6403.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Shibata, D. P. Huynh, and S.-M. Pulst
A novel protein with RNA-binding motifs interacts with ataxin-2
Hum. Mol. Genet., May 22, 2000; 9(9): 1303 - 1313.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Kazantsev, E. Preisinger, A. Dranovsky, D. Goldgaber, and D. Housman
Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells
PNAS, September 28, 1999; 96(20): 11404 - 11409.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
H. Li, S.-H. Li, A. L. Cheng, L. Mangiarini, G. P. Bates, and X.-J. Li
Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice
Hum. Mol. Genet., July 1, 1999; 8(7): 1227 - 1236.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S.-H. Li, A. L. Cheng, H. Li, and X.-J. Li
Cellular Defects and Altered Gene Expression in PC12 Cells Stably Expressing Mutant Huntingtin
J. Neurosci., July 1, 1999; 19(13): 5159 - 5172.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C.-A. Gutekunst, S.-H. Li, H. Yi, J. S. Mulroy, S. Kuemmerle, R. Jones, D. Rye, R. J. Ferrante, S. M. Hersch, and X.-J. Li
Nuclear and Neuropil Aggregates in Huntington's Disease: Relationship to Neuropathology
J. Neurosci., April 1, 1999; 19(7): 2522 - 2534.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P. W. Faber, J. R. Alter, M. E. MacDonald, and A. C. Hart
Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron
PNAS, January 5, 1999; 96(1): 179 - 184.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C.-A. Gutekunst, S.-H. Li, H. Yi, R. J. Ferrante, X.-J. Li, and S. M. Hersch
The Cellular and Subcellular Localization of Huntingtin-Associated Protein 1 (HAP1): Comparison with Huntingtin in Rat and Human
J. Neurosci., October 1, 1998; 18(19): 7674 - 7686.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. S. Hackam, A. S. Yassa, R. Singaraja, M. Metzler, C.-A. Gutekunst, L. Gan, S. Warby, C. L. Wellington, J. Vaillancourt, N. Chen, et al.
Huntingtin Interacting Protein 1 Induces Apoptosis via a Novel Caspase-dependent Death Effector Domain
J. Biol. Chem., December 22, 2000; 275(52): 41299 - 41308.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. Khoshnan, J. Ko, and P. H. Patterson
Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity
PNAS, January 22, 2002; 99(2): 1002 - 1007.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.