2007年7月
Involvement of valosin-containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates
GENES TO CELLS
- ,
- ,
- 巻
- 12
- 号
- 7
- 開始ページ
- 889
- 終了ページ
- 901
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1111/j.1365-2443.2007.01099.x
- 出版者・発行元
- BLACKWELL PUBLISHING
Abnormal protein aggregates are commonly observed in affected neurons in many neurodegenerative disorders. We have reported that valosin-containing protein (VCP) co-localizes with protein aggregates in patients' neurons and in cultured cells expressing diseased proteins. However, the significance of such co-localization remains elucidated. Here we report the involvement of VCP in the re-solubilization process of abnormal protein aggregates. VCP recognized and accumulated onto pre-formed protein aggregates created by proteasome inhibition. VCP knockdown or the expression of dominant-negative VCP both significantly delayed the elimination of ubiquitin-positive aggregates. VCP was involved in the clearance of pre-formed polyglutamine aggregates as well. Paradoxically, VCP knockdown also diminished polyglutamine aggregate formation. Furthermore, its ATPase activity was required for the re-solubilization and re-activation of heat-denatured proteins, such as luciferase, from insoluble aggregates. We thus propose that VCP functions as a mediator for both aggregate formation and clearance depending upon the concentration of soluble aggregate-prone proteins, indicating dual VCP functions as an aggregate formase and an unfoldase.
- リンク情報
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- DOI
- https://doi.org/10.1111/j.1365-2443.2007.01099.x
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902206006563685
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/17584300
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000247440600006&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1111/j.1365-2443.2007.01099.x
- ISSN : 1356-9597
- J-Global ID : 200902206006563685
- PubMed ID : 17584300
- Web of Science ID : WOS:000247440600006