The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
CHIP-Hsc70 Complex Ubiquitinates Phosphorylated Tau and Enhances Cell Survival
Open accessAbstract
The microtubule-binding protein tau has been implicated in the neurofibrillary pathology of Alzheimer's disease. Within affected cells, ubiquitinated and hyperphosphorylated tau assembles into massive filamentous polymers. Eventually these tangle-bearing neurons die. The formation of neurofibrillary tangles closely parallels the progression and anatomic distribution of neuronal loss in Alzheimer's disease, suggesting that these lesions play a role in the disease pathogenesis. Mutations in the human tau gene cause autosomal dominant neurodegenerative disorders. These and other neurodegenerative conditions are also characterized by extensive neurofibrillary pathology. The mechanisms underlying tau-mediated neurotoxicity remain unclear; however, phosphorylated tau is a strong candidate for a toxic molecule, particularly those isoforms phosphorylated by the kinases glycogen synthase kinase 3beta and Cdk5. Here we show that Alzheimer tau binds to Hsc70, and its phosphorylation is a recognition requirement for the addition of ubiquitin (Ub) by the E3 Ub ligase CHIP (carboxyl terminus of the Hsc70-interacting protein) and the E2 conjugating enzyme UbcH5B. Other E3 Ub ligases including parkin and Cbl failed to ubiquitinate phosphorylated tau. CHIP could rescue phosphorylated tau-induced cell death, and therefore the CHIP-Hsc70 complex may provide a new therapeutic target for the tauopathies.
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Cites
Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism
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Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
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The ubiquitin pathway in Parkinson's disease
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A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
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Shimura, H., Schlossmacher, M. G., Hattori, N., Frosch, M. P., Trockenbacher, A., Schneider, R., Mizuno, Y., Kosik, K. S., & Selkoe, D. J. (2001) · Science · doi:10.1126/science.1060627 · Cited by 1,053
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The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation
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Cited by
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Roles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Acetylation of Tau Inhibits Its Degradation and Contributes to Tauopathy
Min, S.-W., Cho, S.-H., Zhou, Y., Schroeder, S., Haroutunian, V., Seeley, W. W., Huang, E. J., Shen, Y., Masliah, E., Mukherjee, C., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.044 · Cited by 949
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899
CHIP and Hsp70 regulate tau ubiquitination, degradation and aggregation
Petrucelli, L. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh083 · Cited by 723
Metadata
- Authors
- Shimura, H., Schwartz, D., Gygi, S. P., & Kosik, K. S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-02
- Volume
- 279
- Issue
- 6
- Pages
- 4869-4876
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1987927755
- Cited by
- 469
- References
- 39
- FWCI
- 21.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
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