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The transcription factor XBP-1 in neurodegenerative diseases
Molecular Neurodegeneration volume 8, Article number: O24 (2013)
Parkinson’s disease (PD) is a neurodegenerative disorder that is either associated with an autosomal dominant or recessive mode of inheritance. The latter forms are mostly linked to mutations in the genes of parkin, Pink-1 and DJ-1. Several lines of evidence indicate that DJ-1 could act as an antioxidant while parkin has been characterized as an ubiquitin-ligase. Parkin was reported to interact physically with DJ-1 monomers in oxidative stress conditions but did not promote its ubiquitin-linked proteasomal degradation. This led us to examine whether parkin could control DJ-1 via its function as transcription factor that we documented recently . We have shown  that parkin controls DJ-1 by a mechanism independent of its ubiquitin-ligase activity and that this regulation is abolished by PD-related pathogenic mutations. Thus, parkin increases DJ-1 promoter trans-activation, mRNA levels and protein expression via a transcriptional cascade involving p53 repression and subsequent activation of ER-stress induced X-box-binding protein-1S (XBP-1S). Then, XBP-1S physically interacts with DJ-1 promoter, thereby raising DJ-1 mRNA and protein levels. Overall, our study unravels a functional dialogue by which parkin and DJ-1 could control ER-stress response in physiopathological conditions. We will discuss the potential involvement of XBP-1 in other neurodegenerative diseases.
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Checler, F., Duplan, E. & Alves da Costa, C. The transcription factor XBP-1 in neurodegenerative diseases. Mol Neurodegeneration 8 (Suppl 1), O24 (2013). https://doi.org/10.1186/1750-1326-8-S1-O24
- Transcription Factor
- Neurodegenerative Disease
- Neurodegenerative Disorder
- Subsequent Activation
- Proteasomal Degradation