Cytoplasmic Ubiquitin-Specific Protease 19 (USP19) Modulates Aggregation of Polyglutamine-Expanded Ataxin-3 and Huntingtin through the HSP90 Chaperone.
- He WT State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Zheng XM State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Zhang YH State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Gao YG State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- Song AX State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- van der Goot FG Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland.
- Hu HY State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
- 2016-01-26
Published in:
- PloS one. - 2016
Ataxin-3
Cytoplasm
Endopeptidases
HEK293 Cells
HSP90 Heat-Shock Proteins
Humans
Huntingtin Protein
Nerve Tissue Proteins
Peptides
Repressor Proteins
Up-Regulation
English
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.
- Language
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- English
- Open access status
- gold
- Identifiers
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- DOI 10.1371/journal.pone.0147515
- PMID 26808260
- Persistent URL
- https://sonar.ch/global/documents/96962
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