serval:BIB_6BC9845695E4
The E3-Ubiquitin Ligase TRIM50 Interacts with HDAC6 and p62, and Promotes the Sequestration and Clearance of Ubiquitinated Proteins into the Aggresome.
10.1371/journal.pone.0040440
000306354700049
22792322
Fusco
C.
author
Micale
L.
author
Egorov
M.
author
Monti
M.
author
D'Addetta
E.V.
author
Augello
B.
author
Cozzolino
F.
author
Calcagnì
A.
author
Fontana
A.
author
Polishchuk
R.S.
author
Didelot
G.
author
Reymond
A.
author
Pucci
P.
author
Merla
G.
author
article
2012
PLoS One
1932-6203
1932-6203
journal
7
7
e40440
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.
eng
60_published
true
University of Lausanne
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