Volume 8 Supplement 1

Molecular Neurodegeneration: Basic biology and disease pathways

Open Access

The transcription factor XBP-1 in neurodegenerative diseases

  • Frédéric Checler1,
  • Eric Duplan1 and
  • Cristine Alves da Costa1
Molecular Neurodegeneration20138(Suppl 1):O24

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

Published: 13 September 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 [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.

Authors’ Affiliations

(1)
IPMC, UMR7275 CNRS/UNSA

References

  1. da Costa , et al: Nature Cell Biology. 2009, 11: 1370-1375. 10.1038/ncb1981.PubMed CentralView ArticlePubMedGoogle Scholar
  2. Duplan , et al: Journal of Cell Science. 2013, 126: 2124-2133. 10.1242/jcs.127340.View ArticlePubMedGoogle Scholar

Copyright

© Checler et al; licensee BioMed Central Ltd. 2013

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.

Advertisement