| Autor: |
Omura, Tomohiro, Kaneko, Masayuki, Okuma, Yasunobu, Orba, Yasuko, Nagashima, Kazuo, Takahashi, Ryosuke, Fujitani, Noboru, Matsumura, Satoshi, Hata, Akihisa, Kubota, Kyoko, Murahashi, Karin, Uehara, Takashi, Nomura, Yasuyuki |
| Předmět: |
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| Zdroj: |
Journal of Neurochemistry; Dec2006, Vol. 99 Issue 6, p1456-1469, 14p, 4 Color Photographs, 6 Black and White Photographs, 2 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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