title: DJ-1 interacts with RACK1 and protects neurons from oxidative-stress-induced apoptosis.
abstract: PD (Parkinson's disease) is a complex disorder that is associated with neuronal loss or dysfunction caused by genetic risks, environmental factors and advanced aging. It has been reported that DJ-1 mutations rendered neurons sensitive to oxidative damage, which led to the onset of familiar PD. However, the molecular mechanism is still unclear. In the present study we show that DJ-1 interacts with RACK1 (receptor of activated C kinase 1) and increases its dimerization and protein stability. The DJ-1 transgene protects cortical neurons from H2O2-induced apoptosis, and this protective effect is abrogated by knocking down RACK1. Similarly, deletion of DJ-1 in cortical neurons increases the sensitivity to H2O2, and the damage can be significantly rescued by DJ-1 or DJ-1/RACK1 co-transfection, but not by RACK1 alone. We observed further that the interaction of DJ-1 and RACK1 is disrupted by H2O2 or MPP+ (1-methyl-4-phenylpyridinium) treatment, and the protein levels of DJ-1 and RACK1 decreased in neurodegenerative disease models. Taken together, the DJ-1-RACK1 complex protects neurons from oxidative stress-induced apoptosis, with the implication that DJ-1 and RACK1 might be novel targets in the treatment of neurodegenerative diseases.
authors.affiliation: *State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: *State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wu
authors.affiliation: *State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: *State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jun-bing
authors.initials: JB
authors.lastname: Wu
authors.affiliation: *State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jizhong
authors.initials: J
authors.lastname: Lou
authors.affiliation: †Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: ‡Department of Neurology and Institute of Neurology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Jian-qing
authors.initials: JQ
authors.lastname: Ding
authors.affiliation: *State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zengqiang
authors.initials: Z
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019556:COS Cells; D002522:Chlorocebus aethiops; D019204:GTP-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010300:Parkinson Disease / Q000503:physiopathology; D000071617:Protein Deglycase DJ-1; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D006861:Hydrogen Peroxide; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D019204:GTP-Binding Proteins