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

Molecular cell | Jul 1, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12150907

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 RIS Download

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

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