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Hatakeyama S, Matsumoto M, Kamura T, Murayama M, Chui DH, Planel E et al.. U-box protein carboxyl terminus of Hsc70-interacting protein (CHIP) mediates poly-ubiquitylation preferentially on four-repeat Tau and is involved in neurodegeneration of tauopathy. J Neurochem 91: 299-307

Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Fukuoka, Japan.
Journal of Neurochemistry (Impact Factor: 4.28). 11/2004; 91(2):299-307. DOI: 10.1111/j.1471-4159.2004.02713.x
Source: PubMed

ABSTRACT

Neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated and ubiquitylated tau, are exhibited at regions where neuronal loss occurs in neurodegenerative diseases; however, the mechanisms of NFT formation remain unknown. Molecular studies of frontotemporal dementia with parkinsonism-17 demonstrated that increasing the ratio of tau with exon 10 insertion induced fibrillar tau accumulation. Here, we show that carboxyl terminus of Hsc70-interacting protein (CHIP), a U-box protein, recognizes the microtubule-binding repeat region of tau and preferentially ubiquitylates four-repeat tau compared with three-repeat tau. Overexpression of CHIP induced the prompt degradation of tau, reduced the formation of detergent-insoluble tau and inhibited proteasome inhibitor-induced cell death. NFT bearing neurons in progressive supranuclear palsy, in which four-repeat tau is a component, showed the accumulation of CHIP. Thus, CHIP is a ubiquitin ligase for four-repeat tau and maintains neuronal survival by regulating the quality control of tau in neurons.

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Available from: Emmanuel Planel, Apr 29, 2015
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    • "This indicates that Sativex ® not only affects autophagy induction, but could also improve the process of autophagosome-lysosome fusion or the lysosomal degradative activity. Tau ubiquitination, however, takes place with the complex CHIP-HSP70, but not with parkin [54] [55] [56]. Therefore, the protective effects of parkin on tau pathology would most likely be mediated by autophagy rather than by the ubiquitin-proteasome system. "

    Full-text · Dataset · May 2015
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    • "The specific sites were Lys 6, 11, 48, 254, 311, and 353. Out of these, Lys 48 was linked to polyubiquitination that serves as the major target site for CHIP [133]. Hsp110 is an important nucleotide exchange factor for Hsp70 that assists protein folding. "
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    • "This indicates that Sativex ® not only affects autophagy induction, but could also improve the process of autophagosome-lysosome fusion or the lysosomal degradative activity. Tau ubiquitination, however, takes place with the complex CHIP-HSP70, but not with parkin [54] [55] [56]. Therefore, the protective effects of parkin on tau pathology would most likely be mediated by autophagy rather than by the ubiquitin-proteasome system. "
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