CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model
Abstract Parkinson’s disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact cont...
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Nature Portfolio
2017
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oai:doaj.org-article:84cb84aaf7d54684b77826a95ef29a7a2021-12-02T11:52:59ZCDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model10.1038/s41598-017-06012-62045-2322https://doaj.org/article/84cb84aaf7d54684b77826a95ef29a7a2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06012-6https://doaj.org/toc/2045-2322Abstract Parkinson’s disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP+-treated neurons. Furthermore, XBP1s was identified as a substrate of CDK5 and that the phosphorylation of XBP1s at the Ser61 residue enhances its nuclear migration, whereas mutation of the residue to alanine substantially reduces its nuclear translocation and activity. Importantly, phosphorylated XBP1s acts as a nuclear transcription factor for multiple target genes, including metabolic-related genes, FosB, and non-coding RNAs. Our findings confirm that the IRE1α/XBP1 pathway is activated in PD, and reveal a novel role of XBP1s in the pathogenesis of PD. This pathway may be a new therapeutic strategy for PD.Feng-Juan JiaoQing-Zhi WangPei ZhangJian-Guo YanZheng ZhangFeng HeQian ZhangZe-Xi LvXiang PengHong-Wei CaiBo TianNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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Medicine R Science Q Feng-Juan Jiao Qing-Zhi Wang Pei Zhang Jian-Guo Yan Zheng Zhang Feng He Qian Zhang Ze-Xi Lv Xiang Peng Hong-Wei Cai Bo Tian CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model |
| description |
Abstract Parkinson’s disease (PD) is an irreversible and progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta. Growing evidence indicates that endoplasmic reticulum stress is a hallmark of PD; however, its exact contribution to the disease process remains poorly understood. Here, we used molecular biology methods and RNA-Seq analysis to explored an unexpected role of spliced X-Box binding protein 1 (XBP1s) in the nervous system. In this study, we determined that the IRE1α/XBP1 pathway is activated in MPP+-treated neurons. Furthermore, XBP1s was identified as a substrate of CDK5 and that the phosphorylation of XBP1s at the Ser61 residue enhances its nuclear migration, whereas mutation of the residue to alanine substantially reduces its nuclear translocation and activity. Importantly, phosphorylated XBP1s acts as a nuclear transcription factor for multiple target genes, including metabolic-related genes, FosB, and non-coding RNAs. Our findings confirm that the IRE1α/XBP1 pathway is activated in PD, and reveal a novel role of XBP1s in the pathogenesis of PD. This pathway may be a new therapeutic strategy for PD. |
| format |
article |
| author |
Feng-Juan Jiao Qing-Zhi Wang Pei Zhang Jian-Guo Yan Zheng Zhang Feng He Qian Zhang Ze-Xi Lv Xiang Peng Hong-Wei Cai Bo Tian |
| author_facet |
Feng-Juan Jiao Qing-Zhi Wang Pei Zhang Jian-Guo Yan Zheng Zhang Feng He Qian Zhang Ze-Xi Lv Xiang Peng Hong-Wei Cai Bo Tian |
| author_sort |
Feng-Juan Jiao |
| title |
CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model |
| title_short |
CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model |
| title_full |
CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model |
| title_fullStr |
CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model |
| title_full_unstemmed |
CDK5-mediated phosphorylation of XBP1s contributes to its nuclear translocation and activation in MPP+-induced Parkinson’s disease model |
| title_sort |
cdk5-mediated phosphorylation of xbp1s contributes to its nuclear translocation and activation in mpp+-induced parkinson’s disease model |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/84cb84aaf7d54684b77826a95ef29a7a |
| work_keys_str_mv |
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