An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin.

Abstract	A putative G protein-coupled transmembrane polypeptide, named Pael receptor, was identified as an interacting protein with Parkin, a gene product responsible for autosomal recessive juvenile Parkinsonism (AR-JP). When overexpressed in cells, this receptor tends to become unfolded, insoluble, and ubiquitinated in vivo. The insoluble Pael receptor leads to unfolded protein-induced cell death. Parkin specifically ubiquitinates this receptor in the presence of ubiquitin-conjugating enzymes resident in the endoplasmic reticulum and promotes the degradation of insoluble Pael receptor, resulting in suppression of the cell death induced by Pael receptor overexpression. Moreover, the insoluble form of Pael receptor accumulates in the brains of AR-JP patients. Here, we show that the unfolded Pael receptor is a substrate of Parkin, the accumulation of which may cause selective neuronal death in AR-JP.
Authors	Y Imai, M Soda, H Inoue, N Hattori, Y Mizuno, R Takahashi
Journal	Cell (Cell) Vol. 105 Issue 7 Pg. 891-902 (Jun 29 2001) ISSN: 0092-8674 [Print] United States
PMID	11439185 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Cysteine Proteinase Inhibitors Receptors, Cell Surface Recombinant Fusion Proteins Ubiquitins lactacystin UBE2L3 protein, human Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases parkin protein Ligases Acetylcysteine
Topics	Acetylcysteine (analogs & derivatives, pharmacology) Brain (cytology, metabolism) Cell Death Cells, Cultured Cysteine Proteinase Inhibitors (pharmacology) Endoplasmic Reticulum (metabolism) Humans Ligases (genetics, metabolism) Microscopy, Fluorescence Parkinsonian Disorders (genetics, metabolism) Precipitin Tests Protein Binding Protein Folding Receptors, Cell Surface (genetics, metabolism) Recombinant Fusion Proteins (metabolism) Two-Hybrid System Techniques Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Ubiquitins (metabolism)

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