Cited by 723Alzheimer's disease research and treatmentsHeat shock proteins researchUbiquitin and proteasome pathways

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CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation

Petrucelli, L.·2004·Human Molecular Genetics

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Abstract

Molecular chaperones, ubiquitin ligases and proteasome impairment have been implicated in several neurodegenerative diseases, including Alzheimer's and Parkinson's disease, which are characterized by accumulation of abnormal protein aggregates (e.g. tau and alpha-synuclein respectively). Here we report that CHIP, an ubiquitin ligase that interacts directly with Hsp70/90, induces ubiquitination of the microtubule associated protein, tau. CHIP also increases tau aggregation. Consistent with this observation, diverse of tau lesions in human postmortem tissue were found to be immunopositive for CHIP. Conversely, induction of Hsp70 through treatment with either geldanamycin or heat shock factor 1 leads to a decrease in tau steady-state levels and a selective reduction in detergent insoluble tau. Furthermore, 30-month-old mice overexpressing inducible Hsp70 show a significant reduction in tau levels. Together these data demonstrate that the Hsp70/CHIP chaperone system plays an important role in the regulation of tau turnover and the selective elimination of abnormal tau species. Hsp70/CHIP may therefore play an important role in the pathogenesis of tauopathies and also represents a potential therapeutic target.

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Kitada, T., Asakawa, S., Hattori, N., Matsumine, H., Yamamura, Y., Minoshima, S., Yokochi, M., Mizuno, Y., & Shimizu, N. (1998) · Nature · doi:10.1038/33416 · Cited by 5,227
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Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498
Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease
Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., & Crowther, R. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90210-9 · Cited by 2,492
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Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474
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Whitesell, L., Mimnaugh, E. G., De Costa, B., Myers, C. E., & Neckers, L. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8324 · Cited by 1,444
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Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371
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Zou, J., Guo, Y., Guettouche, T., Smith, D. F., & Voellmy, R. W. (1998) · Cell · doi:10.1016/s0092-8674(00)81588-3 · Cited by 1,232
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Auluck, P. K., Chan, H. Y. E., Trojanowski, J. Q., Lee, V. M.-Y., & Bonini, N. M. (2002) · Science · doi:10.1126/science.1067389 · Cited by 1,227
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Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.4051 · Cited by 1,134

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Huang, Y., Wu, Z., & Zhou, B. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2042-8 · Cited by 58
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Pappas, B., Yang, Y., Wang, Y., Kim, K., Chung, H. J., Cheung, M., Ngo, K., Shinn, A. H., & Chan, W. K. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.03.015 · Cited by 60
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Sreenivasmurthy, S. G., Iyaswamy, A., Krishnamoorthi, S., Senapati, S., Malampati, S., Zhu, Z., Su, C.-F., Liu, J., Guan, X.-J., Tong, B. C., et al. (2021) · Phytomedicine · doi:10.1016/j.phymed.2021.153887 · Cited by 57
Interactions of the Proteasomal System with Chaperones
Kästle, M., & Grune, T. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-397863-9.00004-3 · Cited by 56
The E3 ubiquitin ligase CHIP in normal cell function and in disease conditions
Wang, T., Wang, W., Wang, Q., Xie, R., LANDAY, A. L., & Chen, D. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14206 · Cited by 58
Dynamic neural and glial responses of a head-specific model for traumatic brain injury in Drosophila
Saikumar, J., Byrns, C. N., Hemphill, M. A., Meaney, D. F., & Bonini, N. M. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2003909117 · Cited by 53
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Huseby, C. J., Hoffman, C. N., Cooper, G. L., Cocuron, J.-C., Alonso, A. P., Thomas, S. N., Yang, A. J., & Kuret, J. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190604 · Cited by 54
“Because ubiquitylation is transient and linked to tau clearance [16, 17], its effects on tau aggregation rate are likely exerted indirectly through control of bulk tau levels.”
Hsp90 Modulation for the Treatment of Alzheimer’s Disease
Zhao, H., Michaelis, M. L., & Blagg, B. S. J. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-394816-8.00001-5 · Cited by 59
Mechanistic Studies Unravel the Complexity Inherent in Tau Aggregation Leading to Alzheimer’s Disease and the Tauopathies
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Tissue-specific landscape of protein aggregation and quality control in an aging vertebrate
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Yu, A., Fox, S. G., Cavallini, A., Kerridge, C., O’Neill, M. J., Wolak, J., Bose, S., & Morimoto, R. I. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007527 · Cited by 55
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Adachi, H., Waza, M., Katsuno, M., Tanaka, F., Doyu, M., & Sobue, G. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00830.x · Cited by 54
Repair or destruction—an intimate liaison between ubiquitin ligases and molecular chaperones in proteostasis
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Viewpoint: Crosstalks between neurofibrillary tangles and amyloid plaque formation
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Authors: Petrucelli, L.
Affiliations: Mayo Clinic in Florida (US)
Corresponding author: Petrucelli, L.
ORCID: Petrucelli, L.
Venue: Human Molecular Genetics
Publisher: Oxford University Press (OUP)
Published: 2004-01-28
Volume: 13
Issue: 7
Pages: 703-714
ISSN: 0964-6906 (ISSN-L)
1460-2083
DOI: 10.1093/hmg/ddh083
OpenAlex: W2168079270
Cited by: 723
References: 41
Citations by year: 2026: 29 · 2025: 36 · 2024: 32 · 2023: 32 · 2022: 37 · 2021: 37 · 2020: 36 · 2019: 25 · 2018: 35 · 2017: 31 · 2016: 31 · 2015: 38 · 2014: 34 · 2013: 28 · 2012: 31
FWCI: 10.76
Type: journal article
Language: en
Open access: closed
Locations: Human Molecular Genetics (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Institute of Neurological Disorders and Stroke (R01NS041816, R01-NS41816-01)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords: CHIP, HSP70, tau protein, ubiquitination, protein degradation, tau aggregation, molecular chaperones, ubiquitin ligase, geldanamycin, heat shock factor 1, tauopathy, Alzheimer's disease, Parkinson's disease, proteasome
MeSH terms: Heat Shock Transcription Factors, Animals, Cell Line, Detergents, DNA-Binding Proteins, Genetic Vectors, Humans, Immunohistochemistry, Lac Operon, Models, Genetic, Mutation, Nuclear Proteins, Protein Binding, Quinones, Subcellular Fractions, Transcription Factors, Transfection, Blotting, Western, Benzoquinones, tau Proteins, Molecular Chaperones, HSP70 Heat-Shock Proteins, Transgenes, COS Cells, Ubiquitin, Drosophila Proteins, Ubiquitin-Protein Ligases, Cell Line, Tumor, Lactams, Macrocyclic, Immunoprecipitation, Mice

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CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation

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