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 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 ala

SUBMITTER: Jiao FJ 

PROVIDER: S-EPMC5514026 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature