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Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.

Mutations in genes encoding both DJ-1 and pten-induced kinase 1 (PINK1) are independently linked to autosomal recessive early-onset familial forms of Parkinson's disease (PD). We here report identification of a family with PD patients harboring novel heterozygous missense mutations in both PINK1 and DJ-1 genes encoding DJ-1A39S and PINK1P399L, respectively. In transfected cells, DJ-1 interacts with PINK1. PINK1P399L is less stable than the wild-type protein and is degraded via the ubiquitin-mediated proteasomal pathway. Expression of wild-type DJ-1 increased steady-state levels of PINK1, whereas expression of DJ-1A39S reduced steady-state levels of PINK1. Furthermore, co-expression of wild-type DJ-1 and PINK1 suppresses neurotoxin 1-methyl-4-phenylpyridinium (MPP(+))-induced death of dopaminergic SH-SY5Y cells. In contrast, co-expression of PD-associated DJ-1A39S and PINK1P399L significantly potentiated susceptibility of SH-SY5Y cells to MPP(+)-induced cell death. This study reports the first case of autosomal recessive PD with digenic inheritance and demonstrates that DJ-1 and PINK1 physically associate and collaborate to protect cells against stress via complex formation.

Pubmed ID: 16632486


  • Tang B
  • Xiong H
  • Sun P
  • Zhang Y
  • Wang D
  • Hu Z
  • Zhu Z
  • Ma H
  • Pan Q
  • Xia JH
  • Xia K
  • Zhang Z


Human molecular genetics

Publication Data

June 1, 2006

Associated Grants


Mesh Terms

  • Adult
  • Age of Onset
  • Amino Acid Sequence
  • Cell Line, Tumor
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Oncogene Proteins
  • Parkinson Disease
  • Pedigree
  • Protein Kinases
  • Sequence Homology, Amino Acid