Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 9 January 1998:
Vol. 279. no. 5348, pp. 242 - 247
DOI: 10.1126/science.279.5348.242
Prev | Table of Contents

Reports

Frameshift Mutants of beta  Amyloid Precursor Protein and Ubiquitin-B in Alzheimer's and Down Patients

Fred W. van Leeuwen, * Dominique P. V. de Kleijn, Helma H. van den Hurk, Andrea Neubauer, Marc A. F. Sonnemans, Jacqueline A. Sluijs, Soner Köycü, Ravindra D. J. Ramdjielal, Ahmad Salehi, Gerard J. M. Martens, Frank G. Grosveld, J. Peter H. Burbach, Elly M. Hol

The cerebral cortex of Alzheimer's and Down syndrome patients is characterized by the presence of protein deposits in neurofibrillary tangles, neuritic plaques, and neuropil threads. These structures were shown to contain forms of beta  amyloid precursor protein and ubiquitin-B that are aberrant (+1 proteins) in the carboxyl terminus. The +1 proteins were not found in young control patients, whereas the presence of ubiquitin-B+1 in elderly control patients may indicate early stages of neurodegeneration. The two species of +1 proteins displayed cellular colocalization, suggesting a common origin, operating at the transcriptional level or by posttranscriptional editing of RNA. This type of transcript mutation is likely an important factor in the widely occurring nonfamilial early- and late-onset forms of Alzheimer's disease.

F. W. van Leeuwen, D. P. V. de Kleijn, A. Neubauer, M. A. F. Sonnemans, J. A. Sluijs, S. Köycü, R. D. J. Ramdjielal, A. Salehi, E. M. Hol, Graduate School for Neurosciences Amsterdam, Netherlands Institute for Brain Research, 1105 AZ Amsterdam, Netherlands.
H. H. van den Hurk and G. J. M. Martens, Department of Molecular Animal Physiology, University of Nijmegen, 6525 ED Nijmegen, Netherlands.
F. G. Grosveld, Department of Cell Biology and Genetics, Erasmus University, 3000 DR Rotterdam, Netherlands.
J. P. H. Burbach, Rudolf Magnus Institute for Neurosciences, 3584 CG Utrecht, Netherlands.
*   To whom correspondence should be addressed. E-mail: f.van.leeuwen{at}nih.knaw.nl

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Stressing the ubiquitin/proteasome system.
N. P. Dantuma and K. Lindsten (2009)
Cardiovasc Res
   Abstract »    Full Text »    PDF »
Ubiquitin degradation with its substrate, or as a monomer in a ubiquitination-independent mode, provides clues to proteasome regulation.
N. Shabek, Y. Herman-Bachinsky, and A. Ciechanover (2009)
PNAS 106, 11907-11912
   Abstract »    Full Text »    PDF »
The HECT Domain of TRIP12 Ubiquitinates Substrates of the Ubiquitin Fusion Degradation Pathway.
Y. Park, S. K. Yoon, and J.-B. Yoon (2009)
J. Biol. Chem. 284, 1540-1549
   Abstract »    Full Text »    PDF »
Minimal length requirement for proteasomal degradation of ubiquitin-dependent substrates.
L. G. G. C. Verhoef, C. Heinen, A. Selivanova, E. F. Halff, F. A. Salomons, and N. P. Dantuma (2009)
FASEB J 23, 123-133
   Abstract »    Full Text »    PDF »
Argyrophilic grain disease.
I. Ferrer, G. Santpere, and F. W. van Leeuwen (2008)
Brain 131, 1416-1432
   Abstract »    Full Text »    PDF »
Dose-dependent inhibition of proteasome activity by a mutant ubiquitin associated with neurodegenerative disease.
P. van Tijn, F. M. S. de Vrij, K. G. Schuurman, N. P. Dantuma, D. F. Fischer, F. W. van Leeuwen, and E. M. Hol (2007)
J. Cell Sci. 120, 1615-1623
   Abstract »    Full Text »    PDF »
Structural and Functional Variations in Human Apolipoprotein E3 and E4.
C.-Y. Chou, W.-P. Jen, Y.-H. Hsieh, M.-S. Shiao, and G.-G. Chang (2006)
J. Biol. Chem. 281, 13333-13344
   Abstract »    Full Text »    PDF »
Beta-amyloid accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system..
C. G. Almeida, R. H. Takahashi, and G. K. Gouras (2006)
J. Neurosci. 26, 4277-4288
   Abstract »    Full Text »    PDF »
hUPF2 Silencing Identifies Physiologic Substrates of Mammalian Nonsense-Mediated mRNA Decay.
J. Wittmann, E. M. Hol, and H.-M. Jack (2006)
Mol. Cell. Biol. 26, 1272-1287
   Abstract »    Full Text »    PDF »
A perspective on sporadic inclusion-body myositis: The role of aging and inflammatory processes.
C. E. Finch (2006)
Neurology 66, S1-S6
   Abstract »    Full Text »    PDF »
Inclusion-body myositis: A myodegenerative conformational disorder associated with A{beta}, protein misfolding, and proteasome inhibition.
V. Askanas and W. K. Engel (2006)
Neurology 66, S39-S48
   Abstract »    Full Text »    PDF »
Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies.
F. W. van Leeuwen, P. van Tijn, M.A.F. Sonnemans, B. Hobo, D. M.A. Mann, C. Van Broeckhoven, S. Kumar-Singh, P. Cras, G. Leuba, A. Savioz, et al. (2006)
Neurology 66, S86-S92
   Abstract »    Full Text »    PDF »
Endoplasmic reticulum stress compromises the ubiquitin-proteasome system.
V. Menendez-Benito, L. G.G.C. Verhoef, M. G. Masucci, and N. P. Dantuma (2005)
Hum. Mol. Genet. 14, 2787-2799
   Abstract »    Full Text »    PDF »
The slow Wallerian degeneration gene, WldS, inhibits axonal spheroid pathology in gracile axonal dystrophy mice.
W. Mi, B. Beirowski, T. H. Gillingwater, R. Adalbert, D. Wagner, D. Grumme, H. Osaka, L. Conforti, S. Arnhold, K. Addicks, et al. (2005)
Brain 128, 405-416
   Abstract »    Full Text »    PDF »
A 17p11.2 germline deletion in a patient with Smith-Magenis syndrome and neuroblastoma.
T Hienonen, H Sammalkorpi, P Isohanni, R Versteeg, R Karikoski, and L A Aaltonen (2005)
J. Med. Genet. 42, e3
   Full Text »    PDF »
Paradoxical homozygous expression from heterozygotes and heterozygous expression from homozygotes as a consequence of transcriptional infidelity through a polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia.
K. F. Benson, R. E. Person, F.-Q. Li, K. Williams, and M. Horwitz (2004)
Nucleic Acids Res. 32, 6327-6333
   Abstract »    Full Text »    PDF »
A survey of RNA editing in human brain.
M. Blow, P. A. Futreal, R. Wooster, and M. R. Stratton (2004)
Genome Res. 14, 2379-2387
   Abstract »    Full Text »    PDF »
Mutant ubiquitin UBB+1 is accumulated in sporadic inclusion-body myositis muscle fibers.
P. Fratta, W. K. Engel, F. W. Van Leeuwen, E. M. Hol, G. Vattemi, and V. Askanas (2004)
Neurology 63, 1114-1117
   Abstract »    Full Text »    PDF »
Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases.
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 (2004)
Hum. Mol. Genet. 13, 1803-1813
   Abstract »    Full Text »    PDF »
Phosphorylation of the Histone Deacetylase 7 Modulates Its Stability and Association with 14-3-3 Proteins.
X. Li, S. Song, Y. Liu, S.-H. Ko, and H.-Y. Kao (2004)
J. Biol. Chem. 279, 34201-34208
   Abstract »    Full Text »    PDF »
Host RNA polymerase II makes minimal contributions to retroviral frame-shift mutations.
J. Zhang (2004)
J. Gen. Virol. 85, 2389-2395
   Abstract »    Full Text »    PDF »
Disease-specific accumulation of mutant ubiquitin as a marker for proteasomal dysfunction in the brain.
D. F. FISCHER, R. A. I. DE VOS, R. VAN DIJK, F. M. S. DE VRIJ, E. A. PROPER, M. A. F. SONNEMANS, M. C. VERHAGE, J. A. SLUIJS, B. HOBO, M. ZOUAMBIA, et al. (2003)
FASEB J 17, 2014-2024
   Abstract »    Full Text »    PDF »
Frameshifted {beta}-Amyloid Precursor Protein (APP+1) Is a Secretory Protein, and the Level of APP+1 in Cerebrospinal Fluid Is Linked to Alzheimer Pathology.
E. M. Hol, R. van Dijk, L. Gerez, J. A. Sluijs, B. Hobo, M. T. Tonk, A. de Haan, W. Kamphorst, D. F. Fischer, R. Benne, et al. (2003)
J. Biol. Chem. 278, 39637-39643
   Abstract »    Full Text »    PDF »
Ubiquitin, Proteasomes, and the Aging Brain.
D. A. Gray, M. Tsirigotis, and J. Woulfe (2003)
Sci. Aging Knowl. Environ. 2003, re6-6
   Abstract »    Full Text »    PDF »
Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates.
K. M. Donaldson, W. Li, K. A. Ching, S. Batalov, C.-C. Tsai, and C. A. P. Joazeiro (2003)
PNAS 100, 8892-8897
   Abstract »    Full Text »    PDF »
Distinct chaperone mechanisms can delay the formation of aggresomes by the myopathy-causing R120G {alpha}B-crystallin mutant.
A. T. Chavez Zobel, A. Loranger, N. Marceau, J. R. Theriault, H. Lambert, and J. Landry (2003)
Hum. Mol. Genet. 12, 1609-1620
   Abstract »    Full Text »    PDF »
Ubiquitylation as a Quality Control System for Intracellular Proteins.
S. Hatakeyama and K. I. Nakayama (2003)
J. Biochem. 134, 1-8
   Abstract »    Full Text »    PDF »
An Iron-responsive Element Type II in the 5'-Untranslated Region of the Alzheimer's Amyloid Precursor Protein Transcript.
J. T. Rogers, J. D. Randall, C. M. Cahill, P. S. Eder, X. Huang, H. Gunshin, L. Leiter, J. McPhee, S. S. Sarang, T. Utsuki, et al. (2002)
J. Biol. Chem. 277, 45518-45528
   Abstract »    Full Text »    PDF »
Transcription and nuclear transport of CAG/CTG trinucleotide repeats in yeast.
E. Fabre, B. Dujon, and G.-F. Richard (2002)
Nucleic Acids Res. 30, 3540-3547
   Abstract »    Full Text »    PDF »
N-Acetylcysteine and Celecoxib Lessen Cadmium Cytotoxicity Which Is Associated with Cyclooxygenase-2 Up-regulation in Mouse Neuronal Cells.
M. E. Figueiredo-Pereira, Z. Li, M. Jansen, and P. Rockwell (2002)
J. Biol. Chem. 277, 25283-25289
   Abstract »    Full Text »    PDF »
Strong aggregation and increased toxicity of polyleucine over polyglutamine stretches in mammalian cells.
J. C. Dorsman, B. Pepers, D. Langenberg, H. Kerkdijk, M. Ijszenga, J. T. den Dunnen, R.A.C. Roos, and G.-J. B. van Ommen (2002)
Hum. Mol. Genet. 11, 1487-1496
   Abstract »    Full Text »    PDF »
Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation.
K. Lindsten, F. M.S. de Vrij, L. G.G.C. Verhoef, D. F. Fischer, F. W. van Leeuwen, E. M. Hol, M. G. Masucci, and N. P. Dantuma (2002)
J. Cell Biol. 157, 417-427
   Abstract »    Full Text »    PDF »
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction.
M. H. Glickman and A. Ciechanover (2002)
Physiol Rev 82, 373-428
   Abstract »    Full Text »    PDF »
Mutant ubiquitin expressed in Alzheimer's disease causes neuronal death1.
F. M. S. DE VRIJ, J. A. SLUIJS, L. GREGORI, D. F. FISCHER, W. T. J. M. C. HERMENS, D. GOLDGABER, J. VERHAAGEN, F. W. VAN LEEUWEN, and E. M. HOL (2001)
FASEB J 15, 2680-2688
   Abstract »    Full Text »    PDF »
Presenilin Binding Protein Is Associated with Neurofibrillary Alterations in Alzheimer's Disease and Stimulates Tau Phosphorylation.
Q. Chen, H. Yoshida, D. Schubert, P. Maher, M. Mallory, and E. Masliah (2001)
Am. J. Pathol. 159, 1597-1602
   Abstract »    Full Text »    PDF »
Milestone or Genomania? The Relevance of the Human Genome Project to Biological Aging and the Age-Related Diseases.
H. T. Blumenthal (2001)
J. Gerontol. A Biol. Sci. Med. Sci. 56, M529-537
   Full Text »    PDF »
Translational misreading: a tRNA modification counteracts a +2 ribosomal frameshift.
D. Bregeon, V. Colot, M. Radman, and F. Taddei (2001)
Genes & Dev. 15, 2295-2306
   Abstract »    Full Text »    PDF »
Gene Regulation in the Magnocellular Hypothalamo-Neurohypophysial System.
J. P. H. Burbach, S. M. Luckman, D. Murphy, and H. Gainer (2001)
Physiol Rev 81, 1197-1267
   Abstract »    Full Text »    PDF »
mRNA mutations of type I protein kinase A regulatory subunit {alpha} in T lymphocytes of a subject with systemic lupus erythematosus.
D. Laxminarayana and G. M. Kammer (2000)
Int. Immunol. 12, 1521-1529
   Abstract »    Full Text »    PDF »
CAG tract of MJD-1 may be prone to frameshifts causing polyalanine accumulation.
C. Gaspar, M. Jannatipour, P. Dion, J. Laganiere, J. Sequeiros, B. Brais, and G. A. Rouleau (2000)
Hum. Mol. Genet. 9, 1957-1966
   Abstract »    Full Text »    PDF »
Molecular misreading in non-neuronal cells.
F. W. VAN LEEUWEN, E. M. HOL, R. W. H. HERMANUSSEN, M. A. F. SONNEMANS, E. MORAAL, D. F. FISCHER, D. A. P. EVANS, K.-F. CHOOI, J. P. H. BURBACH, and D. MURPHY (2000)
FASEB J 14, 1595-1602
   Abstract »    Full Text »
Induction of apoptosis by extracellular ubiquitin in human hematopoietic cells: possible involvement of STAT3 degradation by proteasome pathway in interleukin 6-dependent hematopoietic cells.
H. Daino, I. Matsumura, K. Takada, J. Odajima, H. Tanaka, S. Ueda, H. Shibayama, H. Ikeda, M. Hibi, T. Machii, et al. (2000)
Blood 95, 2577-2585
   Abstract »    Full Text »    PDF »
Causes of Alzheimer's disease.
D. G. Munoz and H. Feldman (2000)
Can. Med. Assoc. J. 162, 65-72
   Abstract »    Full Text »    PDF »
Aberrant Protein Deposition and Neurological Disease.
M. D. Kaytor and S. T. Warren (1999)
J. Biol. Chem. 274, 37507-37510
   Full Text »    PDF »
Tau Pathology Generated by Overexpression of Tau.
I. Grundke-Iqbal and K. Iqbal (1999)
Am. J. Pathol. 155, 1781-1785
   Full Text »    PDF »
Wild-type but not Alzheimer-mutant amyloid precursor protein confers resistance against p53-mediated apoptosis.
X. Xu, D. Yang, T. Wyss-Coray, J. Yan, L. Gan, Y. Sun, and L. Mucke (1999)
PNAS 96, 7547-7552
   Abstract »    Full Text »    PDF »
McArdle's Disease : The Unsolved Mystery of the Reappearing Enzyme.
A. Martinuzzi, G. Schievano, A. Nascimbeni, and M. Fanin (1999)
Am. J. Pathol. 154, 1893-1897
   Abstract »    Full Text »    PDF »
Parkinson's Disease Is Associated with Oxidative Damage to Cytoplasmic DNA and RNA in Substantia Nigra Neurons.
J. Zhang, G. Perry, M. A. Smith, D. Robertson, S. J. Olson, D. G. Graham, and T. J. Montine (1999)
Am. J. Pathol. 154, 1423-1429
   Abstract »    Full Text »    PDF »
Phenotypic Change Caused by Transcriptional Bypass of Uracil in Nondividing Cells.
A. Viswanathan, H. J. You, and P. W. Doetsch (1999)
Science 284, 159-162
   Abstract »    Full Text »
Mutant Membrane Protein Toxicity.
C. Stewart, J. Bailey, and C. Manoil (1998)
J. Biol. Chem. 273, 28078-28084
   Abstract »    Full Text »    PDF »
Unexpected frameshifts from gene to expressed protein in a phage-displayed peptide library.
J. Carcamo, M. W. Ravera, R. Brissette, O. Dedova, J. R. Beasley, A. Alam-Moghe, C. Wan, A. Blume, and W. Mandecki (1998)
PNAS 95, 11146-11151
   Abstract »    Full Text »    PDF »
The Synuclein Family.
C. Lavedan (1998)
Genome Res. 8, 871-880
   Abstract »    Full Text »
Highly Mutagenic Bypass Synthesis by T7 RNA Polymerase of Site-specific Benzo[a]pyrene Diol Epoxide-adducted Template DNA.
K. M. Remington, S. E. Bennett, C. M. Harris, T. M. Harris, and K. Bebenek (1998)
J. Biol. Chem. 273, 13170-13176
   Abstract »    Full Text »    PDF »
Amyloid Protein Precursor Stimulates Excitatory Amino Acid Transport. IMPLICATIONS FOR ROLES IN NEUROPROTECTION AND PATHOGENESIS.
E. Masliah, J. Raber, M. Alford, M. Mallory, M. P. Mattson, D. Yang, D. Wong, and L. Mucke (1998)
J. Biol. Chem. 273, 12548-12554
   Abstract »    Full Text »    PDF »
Stable Complexes Involving Acetylcholinesterase and Amyloid-beta Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer's Fibrils.
A. Alvarez, R. Alarcon, C. Opazo, E. O. Campos, F. J. Munoz, F. H. Calderon, F. Dajas, M. K. Gentry, B. P. Doctor, F. G. De Mello, et al. (1998)
J. Neurosci. 18, 3213-3223
   Abstract »    Full Text »    PDF »
Novel Frameshift Mutations near Short Simple Repeats.
W. H. van den Hurk, H. J. J. Willems, M. Bloemen, and G. J. M. Martens (2001)
J. Biol. Chem. 276, 11496-11498
   Abstract »    Full Text »    PDF »
Inhibition of the ubiquitin-proteasome system in Alzheimer's disease.
Y. A. Lam, C. M. Pickart, A. Alban, M. Landon, C. Jamieson, R. Ramage, R. J. Mayer, and R. Layfield (2000)
PNAS 97, 9902-9906
   Abstract »    Full Text »    PDF »
Formation of high molecular weight complexes of mutant Cu,Zn-superoxide dismutase in a mouse model for familial amyotrophic lateral sclerosis.
J. A. Johnston, M. J. Dalton, M. E. Gurney, and R. R. Kopito (2000)
PNAS 97, 12571-12576
   Abstract »    Full Text »    PDF »
Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degradation substrate that blocks proteasomal degradation.
K. Lindsten, F. M.S. de Vrij, L. G.G.C. Verhoef, D. F. Fischer, F. W. van Leeuwen, E. M. Hol, M. G. Masucci, and N. P. Dantuma (2002)
J. Cell Biol. 157, 417-427
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)