The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome

Carmela Fusco, Lucia Micale, Mikhail Egorov, Maria Monti, Ester Valentina D'Addetta, Bartolomeo Augello, Flora Cozzolino, Alessia Calcagnì, Andrea Fontana, Roman S. Polishchuk, Gerard Didelot, Alexandre Reymond, Piero Pucci, Giuseppe Merla

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Article numbere40440
JournalPLoS One
Volume7
Issue number7
DOIs
Publication statusPublished - Jul 9 2012

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Ubiquitinated Proteins
ubiquitin-protein ligase
Ubiquitin-Protein Ligases
proteasome endopeptidase complex
Proteasome Endopeptidase Complex
histone deacetylase
Proteins
Histone Deacetylases
proteins
autophagy
Autophagy
protein aggregates
Fibroblasts
Ligases
ubiquitin
Ubiquitin
ligases
fibroblasts
Agglomeration
Embryonic Structures

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome. / Fusco, Carmela; Micale, Lucia; Egorov, Mikhail; Monti, Maria; D'Addetta, Ester Valentina; Augello, Bartolomeo; Cozzolino, Flora; Calcagnì, Alessia; Fontana, Andrea; Polishchuk, Roman S.; Didelot, Gerard; Reymond, Alexandre; Pucci, Piero; Merla, Giuseppe.

In: PLoS One, Vol. 7, No. 7, e40440, 09.07.2012.

Research output: Contribution to journalArticle

Fusco, Carmela ; Micale, Lucia ; Egorov, Mikhail ; Monti, Maria ; D'Addetta, Ester Valentina ; Augello, Bartolomeo ; Cozzolino, Flora ; Calcagnì, Alessia ; Fontana, Andrea ; Polishchuk, Roman S. ; Didelot, Gerard ; Reymond, Alexandre ; Pucci, Piero ; Merla, Giuseppe. / The E3-ubiquitin ligase TRIM50 interacts with HDAC6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome. In: PLoS One. 2012 ; Vol. 7, No. 7.
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