期刊
PLOS ONE
卷 7, 期 7, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0040440
关键词
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资金
- MIUR FIRB Project Italian Human ProteomeNet [RBRN07BMCT]
- Jerome Lejeune Foundation
- Ricerca Corrente
- Italian Ministry of Health
- 5x1000 voluntary contributions
- Fondazione Banca del Monte di Foggia Domenico Siniscalco Ceci
- Italian Telethon Foundation [GGP06122]
- Ministero degli Affari Esteri, Direzione Generale per la Promozione e la Cooperazione Culturale
- European Commission anEUploidy Integrated Project [037627]
- Swiss National Science Foundation
- Telethon Electron Microscopy Core Facility (Telethon Grant) [GFP08001]
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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