Cytoplasmic Ubiquitin-Specific Protease 19 USP19 Modulates Aggregation of Polyglutamine-Expanded Ataxin-3 and Huntingtin through the HSP90 ChaperoneReportar como inadecuado




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Ubiquitin-specific protease 19 USP19 is one of the deubiquitinating enzymes DUBs involved in regulating the ubiquitination status of substrate proteins. There are two major isoforms of USP19 with distinct C-termini; the USP19 a isoform has a transmembrane domain for anchoring to the endoplasmic reticulum, while USP19 b contains an EEVD motif. Here, we report that the cytoplasmic isoform USP19 b up-regulates the protein levels of the polyglutamine polyQ-containing proteins, ataxin-3 Atx3 and huntingtin Htt, and thus promotes aggregation of their polyQ-expanded species in cell models. Our data demonstrate that USP19 b may orchestrate the stability, aggregation and degradation of the polyQ-expanded proteins through the heat shock protein 90 HSP90 chaperone system. USP19 b directly interacts with HSP90 through its N-terminal CS CHORD and SGT1-P23 domains. In conjunction with HSP90, the cytoplasmic USP19 may play a key role in triage decision for the disease-related polyQ-expanded substrates, suggesting a function of USP19 in quality control of misfolded proteins by regulating their protein levels.



Autor: Wen-Tian He , Xue-Ming Zheng , Yu-Hang Zhang, Yong-Guang Gao, Ai-Xin Song, Françoise Gisou van der Goot, Hong-Yu Hu

Fuente: http://plos.srce.hr/



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