the e3-ubiquitin ligase trim50 interacts with hdac6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome的e3-ubiquitin连接酶trim50与hdac6 p62,和促进的封存和间隙ubiquitinated aggresome蛋白质.pdfVIP

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the e3-ubiquitin ligase trim50 interacts with hdac6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome的e3-ubiquitin连接酶trim50与hdac6 p62,和促进的封存和间隙ubiquitinated aggresome蛋白质.pdf

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the e3-ubiquitin ligase trim50 interacts with hdac6 and p62, and promotes the sequestration and clearance of ubiquitinated proteins into the aggresome的e3-ubiquitin连接酶trim50与hdac6 p62,和促进的封存和间隙ubiquitinated aggresome蛋白质

The E3-Ubiquitin Ligase TRIM50 Interacts with HDAC6 and p62, and Promotes the Sequestration and Clearance of Ubiquitinated Proteins into the Aggresome 1 1 2 3 1 Carmela Fusco , Lucia Micale , Mikhail Egorov , Maria Monti , Ester Valentina D’Addetta , 1 3 `1 4 2 Bartolomeo Augello , Flora Cozzolino , Alessia Calcagnı , Andrea Fontana , Roman S. Polishchuk , Gerard Didelot5, Alexandre Reymond5, Piero Pucci3, Giuseppe Merla 1* 1 Medical Genetics Unit, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy, 2 Telethon Institute of Genetics and Medicine, Naples, Italy, 3 CEINGE Advanced Biotechnology and Department of Organic Chemistry and Biochemistry, Federico II University, Napoli, Italy, 4 Unit of biostatistics, IRCCS Casa Sollievo Della Sofferenza Hospital, San Giovanni Rotondo, Italy, 5 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland 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