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A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin.

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/17141

Title: A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin.
Authors: Omura, Tomohiro Browse this author
Kaneko, Masayuki Browse this author
Okuma, Yasunobu Browse this author
Orba, Yasuko Browse this author
Nagashima, Kazuo Browse this author
Takahashi, Ryosuke Browse this author
Fujitani, Noboru Browse this author
Matsumura, Satoshi Browse this author
Hata, Akihisa Browse this author
Kubota, Kyoko Browse this author
Murahashi, Karin Browse this author
Uehara, Takashi Browse this author
Nomura, Yasuyuki Browse this author
Issue Date: Dec-2006
Publisher: Blackwell Publishing
Journal Title: Journal of Neurochemistry
Volume: 99
Issue: 6
Start Page: 1456
End Page: 1469
Publisher DOI: 10.1111/j.1471-4159.2006.04155.x
PMID: 17059562
Abstract: It has been proposed that in autosomal recessive juvenile parkinsonism (AR-JP), a ubiquitin ligase (E3) Parkin, which is involved in endoplasmic reticulum-associated degradation (ERAD), lacks E3 activity. The resulting accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), a substrate of Parkin, leads to endoplasmic reticulum stress, causing neuronal death. We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress-induced apoptosis. This study shows that HRD1 was expressed in substantia nigra pars compacta (SNC) dopaminergic neurons and interacted with Pael-R through the HRD1 proline-rich region, promoting the ubiquitylation and degradation of Pael-R. Furthermore, the disruption of endogenous HRD1 by small interfering RNA (siRNA) induced Pael-R accumulation and caspase-3 activation. We also found that ATF6 overexpression, which induced HRD1, accelerated and caused Pael-R degradation; the suppression of HRD1 expression by siRNA partially prevents this degradation. These results suggest that in addition to Parkin, HRD1 is also involved in the degradation of Pael-R.
Rights: For full bibliographic citation, please refer to the version available at www.blackwell-synergy.com
Type: article (author version)
URI: http://hdl.handle.net/2115/17141
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 野村 靖幸

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