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 (78)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Verhoef, L. G.G.C.
Right arrow Articles by Dantuma, N. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Verhoef, L. G.G.C.
Right arrow Articles by Dantuma, N. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2002, Vol. 11, No. 22 2689-2700
© 2002 Oxford University Press

Aggregate formation inhibits proteasomal degradation of polyglutamine proteins

Lisette G.G.C. Verhoef, Kristina Lindsten, Maria G. Masucci and Nico P. Dantuma*

Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden

Received May 7, 2002; Accepted August 8, 2002

Insoluble protein aggregates are consistently found in neurodegenerative disorders caused by expanded polyglutamine [poly(Q)] repeats. The aggregates contain various components of the ubiquitin/proteasome system, suggesting an attempt of the cell to clear the aberrant substrate. To investigate the effect of expanded poly(Q) repeats on ubiquitin/proteasome-dependent proteolysis, we targeted these proteins for proteasomal degradation by the introduction of an N-end rule degradation signal. While soluble poly(Q) proteins were degraded, they resisted proteasomal degradation once present in the aggregates. Stabilization was also observed for proteins that are co-aggregated via interaction with the expanded poly(Q) domain. Introduction of a degradation signal in ataxin-1/Q92 reduced the incidence of nuclear inclusions and the cellular toxicity, conceivably by accelerating the clearance of the soluble substrate.

* To whom correspondence should be addressed. Tel: +46 87287147; Fax: +46 8331399; Email: nico.dantuma{at}mtc.ki.se


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
B. Catalgol, I. Ziaja, N. Breusing, T. Jung, A. Hohn, B. Alpertunga, P. Schroeder, N. Chondrogianni, E. S. Gonos, I. Petropoulos, et al.
The Proteasome Is an Integral Part of Solar Ultraviolet A Radiation-induced Gene Expression
J. Biol. Chem., October 30, 2009; 284(44): 30076 - 30086.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
M. Raspe, J. Gillis, H. Krol, S. Krom, K. Bosch, H. van Veen, and E. Reits
Mimicking proteasomal release of polyglutamine peptides initiates aggregation and toxicity
J. Cell Sci., September 15, 2009; 122(18): 3262 - 3271.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. J. Maynard, C. Bottcher, Z. Ortega, R. Smith, B. I. Florea, M. Diaz-Hernandez, P. Brundin, H. S. Overkleeft, J.-Y. Li, J. J. Lucas, et al.
Accumulation of ubiquitin conjugates in a polyglutamine disease model occurs without global ubiquitin/proteasome system impairment
PNAS, August 18, 2009; 106(33): 13986 - 13991.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
N. P. Dantuma and K. Lindsten
Stressing the ubiquitin/proteasome system
Cardiovasc Res, August 11, 2009; (2009) cvp255v2.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
F. A. Salomons, V. Menendez-Benito, C. Bottcher, B. A. McCray, J. P. Taylor, and N. P. Dantuma
Selective Accumulation of Aggregation-Prone Proteasome Substrates in Response to Proteotoxic Stress
Mol. Cell. Biol., April 1, 2009; 29(7): 1774 - 1785.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Mitra, A. S. Tsvetkov, and S. Finkbeiner
Single Neuron Ubiquitin-Proteasome Dynamics Accompanying Inclusion Body Formation in Huntington Disease
J. Biol. Chem., February 13, 2009; 284(7): 4398 - 4403.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
L. G. G. C. Verhoef, C. Heinen, A. Selivanova, E. F. Halff, F. A. Salomons, and N. P. Dantuma
Minimal length requirement for proteasomal degradation of ubiquitin-dependent substrates
FASEB J, January 1, 2009; 23(1): 123 - 133.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
J. Wang, C.-E. Wang, A. Orr, S. Tydlacka, S.-H. Li, and X.-J. Li
Impaired ubiquitin-proteasome system activity in the synapses of Huntington's disease mice
J. Cell Biol., March 24, 2008; 180(6): 1177 - 1189.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Sano, S. Tokudome, N. Shimizu, N. Yoshikawa, C. Ogawa, K. Shirakawa, J. Endo, T. Katayama, S. Yuasa, M. Ieda, et al.
Intramolecular Control of Protein Stability, Subnuclear Compartmentalization, and Coactivator Function of Peroxisome Proliferator-activated Receptor {gamma} Coactivator 1{alpha}
J. Biol. Chem., August 31, 2007; 282(35): 25970 - 25980.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
H. J. Kwun, S. R. da Silva, I. M. Shah, N. Blake, P. S. Moore, and Y. Chang
Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing
J. Virol., August 1, 2007; 81(15): 8225 - 8235.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. A. Bodner, T. F. Outeiro, S. Altmann, M. M. Maxwell, S. H. Cho, B. T. Hyman, P. J. McLean, A. B. Young, D. E. Housman, and A. G. Kazantsev
From the Cover: Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's diseases.
PNAS, March 14, 2006; 103(11): 4246 - 4251.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
J. S. Bett, G. M. Goellner, B. Woodman, G. Pratt, M. Rechsteiner, and G. P. Bates
Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington's disease mice: exclusion of proteasome activator REG{gamma} as a therapeutic target
Hum. Mol. Genet., January 1, 2006; 15(1): 33 - 44.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
V. Menendez-Benito, L. G.G.C. Verhoef, M. G. Masucci, and N. P. Dantuma
Endoplasmic reticulum stress compromises the ubiquitin-proteasome system
Hum. Mol. Genet., October 1, 2005; 14(19): 2787 - 2799.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Rangone, R. Pardo, E. Colin, J.-A. Girault, F. Saudou, and S. Humbert
Phosphorylation of Arfaptin 2 at Ser260 by Akt Inhibits PolyQ-huntingtin-induced Toxicity by Rescuing Proteasome Impairment
J. Biol. Chem., June 10, 2005; 280(23): 22021 - 22028.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. B. Bowman, S.-Y. Yoo, N. P. Dantuma, and H. Y. Zoghbi
Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation
Hum. Mol. Genet., March 1, 2005; 14(5): 679 - 691.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
R. de Pril, D. F. Fischer, M. L.C. Maat-Schieman, B. Hobo, R. A.I. de Vos, E. R. Brunt, E. M. Hol, R. A.C. Roos, and F. W. van Leeuwen
Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases
Hum. Mol. Genet., August 15, 2004; 13(16): 1803 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Abu-Baker, C. Messaed, J. Laganiere, C. Gaspar, B. Brais, and G. A. Rouleau
Involvement of the ubiquitin-proteasome pathway and molecular chaperones in oculopharyngeal muscular dystrophy
Hum. Mol. Genet., October 16, 2003; 12(20): 2609 - 2623.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
A. Michalik and C. Van Broeckhoven
Pathogenesis of polyglutamine disorders: aggregation revisited
Hum. Mol. Genet., October 15, 2003; 12(90002): R173 - 186.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
L. M. Mandrusiak, L. K. Beitel, X. Wang, T. C. Scanlon, E. Chevalier-Larsen, D. E. Merry, and M. A. Trifiro
Transglutaminase potentiates ligand-dependent proteasome dysfunction induced by polyglutamine-expanded androgen receptor
Hum. Mol. Genet., July 1, 2003; 12(13): 1497 - 1506.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. L. Webb, B. Ravikumar, J. Atkins, J. N. Skepper, and D. C. Rubinsztein
{alpha}-Synuclein Is Degraded by Both Autophagy and the Proteasome
J. Biol. Chem., June 27, 2003; 278(27): 25009 - 25013.
[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.