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Prefoldin Plays a Role as a Clearance Factor in Preventing Proteasome Inhibitor-induced Protein Aggregation
| Title: | Prefoldin Plays a Role as a Clearance Factor in Preventing Proteasome Inhibitor-induced Protein Aggregation |
| Authors: | Abe, Akira Browse this author | | Takahashi-Niki, Kazuko Browse this author →KAKEN DB | | Takekoshi, Yuka Browse this author | | Shimizu, Takashi Browse this author | | Kitaura, Hirotake Browse this author →KAKEN DB | | Maita, Hiroshi Browse this author →KAKEN DB | | Iguchi-Ariga, Sanae M. M. Browse this author →KAKEN DB | | Ariga, Hiroyoshi Browse this author →KAKEN DB |
| Issue Date: | 27-Sep-2013 |
| Publisher: | Amer soc biochemistry molecular biology inc |
| Journal Title: | Journal of biological chemistry |
| Volume: | 288 |
| Issue: | 39 |
| Start Page: | 27764 |
| End Page: | 27776 |
| Publisher DOI: | 10.1074/jbc.M113.476358 |
| PMID: | 23946485 |
| Abstract: | Prefoldin is a molecular chaperone composed of six subunits, PFD1-6, and prevents misfolding of newly synthesized nascent polypeptides. Although it is predicted that prefoldin, like other chaperones, modulates protein aggregation, the precise function of prefoldin against protein aggregation under physiological conditions has never been elucidated. In this study, we first established an anti-prefoldin monoclonal antibody that recognizes the prefoldin complex but not its subunits. Using this antibody, it was found that prefoldin was localized in the cytoplasm with dots in co-localization with polyubiquitinated proteins and that the number and strength of dots were increased in cells that had been treated with lactacystin, a proteasome inhibitor, and thapsigargin, an inducer of endoplasmic reticulum stress. Knockdown of prefoldin increased the level of SDS-insoluble ubiquitinated protein and reduced cell viability in lactacystin and thapsigargin-treated cells. Opposite results were obtained in prefoldin-overexpressed cells. It has been reported that mice harboring a missense mutation L110R of MM-1 alpha/PFD5 exhibit neurodegeneration in the cerebellum. Although the prefoldin complex containing L110R MM-1 alpha was properly formed in vitro and in cells derived from L110R MM-1 alpha mice, the levels of ubiquitinated proteins and cytotoxicity were higher in L110R MM-1 alpha cells than in wild-type cells under normal conditions and were increased by lactacystin and thapsigargin treatment, and growth of L110R MM-1 alpha cells was attenuated. Furthermore, the polyubiquitinated protein aggregation level was increased in the brains of L110R MM-1 alpha mice. These results suggest that prefoldin plays a role in quality control against protein aggregation and that dysfunction of prefoldin is one of the causes of neurodegenerative diseases. |
| Rights: | This research was originally published in the Journal of biological chemistry. Abe A, et al. Prefoldin plays a role as a clearance factor in preventing proteasome inhibitor-induced protein aggregation. The Journal of biological chemistry. 2013; 288(39):27764-76. ©2013 the American Society for Biochemistry and Molecular Biology. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/54874 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 有賀 寛芳
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