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  • Oral presentation
  • Open Access

The transcription factor XBP-1 in neurodegenerative diseases

  • 1,
  • 1 and
  • 1
Molecular Neurodegeneration20138 (Suppl 1) :O24

  • Published:


  • Transcription Factor
  • Neurodegenerative Disease
  • Neurodegenerative Disorder
  • Subsequent Activation
  • Proteasomal Degradation

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

IPMC, UMR7275 CNRS/UNSA, Valbonne, France


  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