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- Title
An E3 ubiquitin ligase, Synoviolin, is involved in the degradation of immature nicastrin, and regulates the production of amyloid β-protein.
- Authors
Maeda, Tomoji; Marutani, Toshihiro; Kun Zou; Araki, Wataru; Tanabe, Chiaki; Yagishita, Naoko; Yamano, Yoshihisa; Amano, Tetsuya; Michikawa, Makoto; Nakajima, Toshihiro; Komano, Hiroto
- Abstract
The presenilin complex, consisting of presenilin, nicastrin, anterior pharynx defective-1 and presenilin enhancer-2, constitutes γ-secretase, which is required for the generation of amyloid β-protein. In this article, we show that Synoviolin (also called Hrd1), which is an E3 ubiquitin ligase implicated in endoplasmic reticulum-associated degradation, is involved in the degradation of endogenous immature nicastrin, and affects amyloid β-protein generation. It was found that the level of immature nicastrin was dramatically increased in synoviolin-null cells as a result of the inhibition of degradation, but the accumulation of endogenous presenilin, anterior pharynx defective-1 and presenilin enhancer-2 was not changed. This was abolished by the transfection of exogenous Synoviolin. Moreover, nicastrin was co-immunoprecipitated with Synoviolin, strongly suggesting that nicastrin is the substrate of Synoviolin. Interestingly, amyloid β-protein generation was increased by the overexpression of Synoviolin, although the nicastrin level was decreased. Thus, Synoviolin-mediated ubiquitination is involved in the degradation of immature nicastrin, and probably regulates amyloid β-protein generation. Structured digital abstract • : Synoviolin (uniprotkb: ) physically interacts ( ) with NCT (uniprotkb: ) by anti tag coimmunoprecipitation ( ) • : Ubiquitin (uniprotkb: ) physically interacts ( ) with NCT (uniprotkb: ) by anti bait coimmunoprecipitation ( ) • : NCT (uniprotkb: ) physically interacts ( ) with Synoviolin (uniprotkb: ) by anti bait coimmunoprecipitation ( )
- Subjects
GLYCOPROTEINS; AMYLOID; GENETIC transformation; PROTEINS; NUCLEIC acids
- Publication
FEBS Journal, 2009, Vol 276, Issue 20, p5832
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2009.07264.x