DOI: 10.1111/j.1365-2443.2007.01099.x. Involvement of valosin‐containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates

Involvement of valosin‐containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates

10.1111/j.1365-2443.2007.01099.x

Crossref journal-article

Wiley

Genes to Cells (311)

Abstract

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.

Bibliography

Kobayashi, T., Manno, A., & Kakizuka, A. (2007). Involvement of valosinâcontaining protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates. Genes to Cells, 12(7), 889â901. Portico.

Authors 3

Taeko Kobayashi (first)
Atsushi Manno (additional)
Akira Kakizuka (additional)

References 26 Referenced 81

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Dates

Type	When
Created	18 years, 2 months ago (June 20, 2007, 6:08 a.m.)
Deposited	1 year, 11 months ago (Sept. 28, 2023, 3:20 p.m.)
Indexed	2 months ago (July 2, 2025, 2:33 p.m.)
Issued	18 years, 2 months ago (June 20, 2007)
Published	18 years, 2 months ago (June 20, 2007)
Published Online	18 years, 2 months ago (June 20, 2007)
Published Print	18 years, 2 months ago (July 1, 2007)

Funders 0

None

BibTeX

@article{Kobayashi_2007, title={Involvement of valosin‐containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates}, volume={12}, ISSN={1365-2443}, url={http://dx.doi.org/10.1111/j.1365-2443.2007.01099.x}, DOI={10.1111/j.1365-2443.2007.01099.x}, number={7}, journal={Genes to Cells}, publisher={Wiley}, author={Kobayashi, Taeko and Manno, Atsushi and Kakizuka, Akira}, year={2007}, month=jun, pages={889–901} }

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