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

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.

Pubmed ID: 12150907

Authors

  • Imai Y
  • Soda M
  • Hatakeyama S
  • Akagi T
  • Hashikawa T
  • Nakayama KI
  • Takahashi R

Journal

Molecular cell

Publication Data

July 1, 2002

Associated Grants

None

Mesh Terms

  • Animals
  • Blotting, Western
  • Cell Death
  • Endoplasmic Reticulum
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins
  • Humans
  • Ligases
  • Macromolecular Substances
  • Male
  • Mice
  • Models, Biological
  • Parkinsonian Disorders
  • Protein Binding
  • Protein Folding
  • Protein Transport
  • Rats
  • Rats, Wistar
  • Substantia Nigra
  • Transfection
  • Tumor Cells, Cultured
  • Ubiquitin-Protein Ligases