| Title |
The E3-Ubiquitin Ligase TRIM50 Interacts with HDAC6 and p62, and Promotes the Sequestration and Clearance of Ubiquitinated Proteins into the Aggresome
|
|---|---|
| Published in |
PLOS ONE, July 2012
|
| DOI | 10.1371/journal.pone.0040440 |
| Pubmed ID | |
| Authors |
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 |
| 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. |
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 90 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 3 | 3% |
| Portugal | 1 | 1% |
| Unknown | 86 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 29 | 32% |
| Researcher | 22 | 24% |
| Student > Master | 12 | 13% |
| Student > Bachelor | 3 | 3% |
| Other | 3 | 3% |
| Other | 8 | 9% |
| Unknown | 13 | 14% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 41 | 46% |
| Biochemistry, Genetics and Molecular Biology | 23 | 26% |
| Medicine and Dentistry | 4 | 4% |
| Business, Management and Accounting | 1 | 1% |
| Immunology and Microbiology | 1 | 1% |
| Other | 3 | 3% |
| Unknown | 17 | 19% |