Gene interactions and pathways from curated databases and text-mining
Mol Cell 2002, PMID: 12150907

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

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.

Diseases/Pathways annotated by Medline MESH: Parkinsonian Disorders
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Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Biogrid Interaction: PARK2 — STUB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PARK2 — STUB1 (direct interaction, pull down)
  • IRef Biogrid Interaction: GPR37 — STUB1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HSPA1A — PARK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: HSPA1A — PARK2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PARK2 — PSMA1 (direct interaction, pull down)
  • IRef Biogrid Interaction: PARK2 — UBE2D2 (direct interaction, pull down)
  • IRef Biogrid Interaction: PARK2 — UBE2G2 (direct interaction, pull down)
  • IRef Biogrid Interaction: GPR37 — HSPA8 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: GPR37 — DNAJA1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PARK2 — UBE2J1 (direct interaction, pull down)
  • IRef Biogrid Interaction: DNAJB1 — GPR37 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: HSPA1A — STUB1 (direct interaction, pull down)
  • IRef Biogrid Interaction: GPR37 — PARK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: GPR37 — PARK2 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: PARK2 — HSPA8 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PARK2 — HSPA8 (direct interaction, pull down)
  • IRef Biogrid Interaction: DNAJA1 — PARK2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: GPR37 — HSPA1A (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: GPR37 — HSPA1A (direct interaction, pull down)
  • IRef Biogrid Interaction: DNAJB1 — PARK2 (physical association, affinity chromatography technology)
  • Gene Ontology Complexes ubiquitin ligase complex: ubiquitin ligase complex complex (WWP2-RNF11-UBE2D2-TSPAN17-HSPA1A-DYRK2-CBLL1-CBX8-GPR37-TOPORS-SUGT1-FBXL7-MIB2-FBXL12-FBXO25-FBXW4-ARIH1-TRAF7-BRCC3-UBE2E1-BRAP-UBR2-RNF20-UBE4A-DNAJA1-FBXL4-RING1-RNF144B-RNF8-RNF2-UBE2L3)
  • IRef Hprd Interaction: GPR37 — STUB1 (in vitro)
  • IRef Hprd Interaction: Complex of 51 proteins (in vivo)
  • IRef Hprd Interaction: GPR37 — PARK2 (in vitro)
  • IRef Hprd Interaction: GPR37 — PARK2 (in vivo)
  • IRef Ophid Interaction: GPR37 — STUB1 (aggregation, confirmational text mining)
In total, 480 gene pairs are associated to this article in curated databases