CHIP is associated with Parkin, a gene responsible for familial Parkinson's Disease, and enhances its ubiquitin ligase activity

Yuzuru Imai, Mariko Soda, Shigetsugu Hatakeyama, Takumi Akagi, Tsutomu Hashikawa, Kei Ichi Nakayama, Ryosuke Takahashi

研究成果: ジャーナルへの寄稿記事

385 引用 (Scopus)

抄録

Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.

元の言語英語
ページ(範囲)55-67
ページ数13
ジャーナルMolecular Cell
10
発行部数1
DOI
出版物ステータス出版済み - 1 1 2002

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Endoplasmic Reticulum Stress
Ubiquitination
Ligases
Ubiquitin
Parkinson Disease
Ubiquitin-Protein Ligases
Dopaminergic Neurons
Endoplasmic Reticulum
Genes
Cell Death
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

これを引用

CHIP is associated with Parkin, a gene responsible for familial Parkinson's Disease, and enhances its ubiquitin ligase activity. / Imai, Yuzuru; Soda, Mariko; Hatakeyama, Shigetsugu; Akagi, Takumi; Hashikawa, Tsutomu; Nakayama, Kei Ichi; Takahashi, Ryosuke.

:: Molecular Cell, 巻 10, 番号 1, 01.01.2002, p. 55-67.

研究成果: ジャーナルへの寄稿記事

Imai, Yuzuru ; Soda, Mariko ; Hatakeyama, Shigetsugu ; Akagi, Takumi ; Hashikawa, Tsutomu ; Nakayama, Kei Ichi ; Takahashi, Ryosuke. / CHIP is associated with Parkin, a gene responsible for familial Parkinson's Disease, and enhances its ubiquitin ligase activity. :: Molecular Cell. 2002 ; 巻 10, 番号 1. pp. 55-67.
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abstract = "Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.",
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AU - Imai, Yuzuru

AU - Soda, Mariko

AU - Hatakeyama, Shigetsugu

AU - Akagi, Takumi

AU - Hashikawa, Tsutomu

AU - Nakayama, Kei Ichi

AU - Takahashi, Ryosuke

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N2 - Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.

AB - Unfolded Pael receptor (Pael-R) is a substrate of the E3 ubiquitin ligase Parkin. Accumulation of Pael-R in the endoplasmic reticulum (ER) of dopaminergic neurons induces ER stress leading to neurodegeneration. Here, we show that CHIP, Hsp70, Parkin, and Pael-R formed a complex in vitro and in vivo. The amount of CHIP in the complex was increased during ER stress. CHIP promoted the dissociation of Hsp70 from Parkin and Pael-R, thus facilitating Parkin-mediated Pael-R ubiquitination. Moreover, CHIP enhanced Parkin-mediated in vitro ubiquitination of Pael-R in the absence of Hsp70. Furthermore, CHIP enhanced the ability of Parkin to inhibit cell death induced by Pael-R. Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity.

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