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

Shigetsugu Hatakeyama, Masaki Matsumoto, Takumi Kamura, Miyuki Murayama, Du Hua Chui, Emmanuel Planel, Ryosuke Takahashi, Keiichi I. Nakayama, Akihiko Takashima

研究成果: ジャーナルへの寄稿記事

88 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)299-307
ページ数9
ジャーナルJournal of Neurochemistry
91
発行部数2
DOI
出版物ステータス出版済み - 10 1 2004

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HSC70 Heat-Shock Proteins
Tauopathies
Ubiquitination
Neurofibrillary Tangles
Proteins
Neurons
Microtubule Proteins
Progressive Supranuclear Palsy
Bearings (structural)
Frontotemporal Dementia
Proteasome Inhibitors
Neurodegenerative diseases
Ligases
Ubiquitin
Neurodegenerative Diseases
Quality Control
Detergents
Exons
Cell death
Cell Death

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

これを引用

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. / Hatakeyama, Shigetsugu; Matsumoto, Masaki; Kamura, Takumi; Murayama, Miyuki; Chui, Du Hua; Planel, Emmanuel; Takahashi, Ryosuke; Nakayama, Keiichi I.; Takashima, Akihiko.

:: Journal of Neurochemistry, 巻 91, 番号 2, 01.10.2004, p. 299-307.

研究成果: ジャーナルへの寄稿記事

Hatakeyama, Shigetsugu ; Matsumoto, Masaki ; Kamura, Takumi ; Murayama, Miyuki ; Chui, Du Hua ; Planel, Emmanuel ; Takahashi, Ryosuke ; Nakayama, Keiichi I. ; Takashima, Akihiko. / 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. :: Journal of Neurochemistry. 2004 ; 巻 91, 番号 2. pp. 299-307.
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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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AU - Kamura, Takumi

AU - Murayama, Miyuki

AU - Chui, Du Hua

AU - Planel, Emmanuel

AU - Takahashi, Ryosuke

AU - Nakayama, Keiichi I.

AU - Takashima, Akihiko

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AB - 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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