He WT Zheng XM Zhang YH Gao YG Song AX van der Goot FG Hu HY 2016 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. application/pdf https://sonar.ch/global/documents/96962 eng info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0147515 info:eu-repo/semantics/altIdentifier/pmid/26808260 info:eu-repo/semantics/openAccess PloS one. - 2016 Ataxin-3 Cytoplasm Endopeptidases HEK293 Cells HSP90 Heat-Shock Proteins Humans Huntingtin Protein Nerve Tissue Proteins Peptides Repressor Proteins Up-Regulation Cytoplasmic Ubiquitin-Specific Protease 19 (USP19) Modulates Aggregation of Polyglutamine-Expanded Ataxin-3 and Huntingtin through the HSP90 Chaperone. http://purl.org/coar/resource_type/c_6501