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

Research output: Contribution to journalArticlepeer-review

395 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)55-67
Number of pages13
JournalMolecular Cell
Volume10
Issue number1
DOIs
Publication statusPublished - Jan 1 2002

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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