| 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)
|
