The E3-Ubiquitin Ligase TRIM50 Interacts with HDAC6 and p62, and Promotes the Sequestration and Clearance of Ubiquitinated Proteins into the Aggresome.

Details

Ressource 1Download: BIB_6BC9845695E4.P001.pdf (3838.22 [Ko])
State: Public
Version: author
Serval ID
serval:BIB_6BC9845695E4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The E3-Ubiquitin Ligase TRIM50 Interacts with HDAC6 and p62, and Promotes the Sequestration and Clearance of Ubiquitinated Proteins into the Aggresome.
Journal
PLoS One
Author(s)
Fusco C., Micale L., Egorov M., Monti M., D'Addetta E.V., Augello B., Cozzolino F., Calcagnì A., Fontana A., Polishchuk R.S., Didelot G., Reymond A., Pucci P., Merla G.
ISSN
1932-6203 (Electronic)
ISSN-L
1932-6203
Publication state
Published
Issued date
2012
Volume
7
Number
7
Pages
e40440
Language
english
Abstract
In this study we report that, in response to proteasome inhibition, the E3-Ubiquitin ligase TRIM50 localizes to and promotes the recruitment and aggregation of polyubiquitinated proteins to the aggresome. Using Hdac6-deficient mouse embryo fibroblasts (MEF) we show that this localization is mediated by the histone deacetylase 6, HDAC6. Whereas Trim50-deficient MEFs allow pinpointing that the TRIM50 ubiquitin-ligase regulates the clearance of polyubiquitinated proteins localized to the aggresome. Finally we demonstrate that TRIM50 colocalizes, interacts with and increases the level of p62, a multifunctional adaptor protein implicated in various cellular processes including the autophagy clearance of polyubiquitinated protein aggregates. We speculate that when the proteasome activity is impaired, TRIM50 fails to drive its substrates to the proteasome-mediated degradation, and promotes their storage in the aggresome for successive clearance.
Pubmed
Web of science
Open Access
Yes
Create date
18/08/2012 10:12
Last modification date
20/08/2019 14:25
Usage data