Skip to main content
  • Oral presentation
  • Open access
  • Published:

The transcription factor XBP-1 in neurodegenerative diseases

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 [1]. We have shown [2] 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.

References

  1. da Costa , et al: Nature Cell Biology. 2009, 11: 1370-1375. 10.1038/ncb1981.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Duplan , et al: Journal of Cell Science. 2013, 126: 2124-2133. 10.1242/jcs.127340.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1750-1326-8-S1-O24

Keywords