Document Detail


DJ-1 Promotes the Proteasomal Degradation of Fis1: Implication of DJ-1 in the Neuronal Protection.
MedLine Citation:
PMID:  22871147     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Mutations in DJ-1/PARK7 have been identified as a cause of autosomal-recessive Parkinson's disease (PD) and the antioxidant property of DJ-1 has been shown to be involved in the regulation of mitochondrial function and neuronal cell survival. In this study, we first found that DJ-1 transgene mitigated MPTP-induced DA neuron cell death and cell loss. We then observed that the protein levels of DJ-1 were significantly decreased, whereas levels of Fis1 were noticeably increased in the striatum of MPTP-treated mice. In addition to our identification of RNF5 as an E3-ligase for Fis1 ubiquitination, we demonstrated the DJ-1/Akt/RNF5 signaling pathway's involvement in the regulation of Fis1 proteasomal degradation. In other experiments, we found that Akt1 enhances the mitochondrial translocation and E3-ligase activity of RNF5 leading to the Fis1 degradation. Together, the identification of Fis1 degradation by DJ-1 signaling in the regulation of oxidative stress-induced neuronal cell death supplies a novel mechanism of DJ-1 in neuronal protection with the implication of DJ-1 in a potential therapeutic avenue for Parkinson's diseases.
Authors:
Qiang Zhang; Junbing Wu; Rong Wu; Jun Ma; Guiping Du; Renjie Jiao; Yong Tian; Zheng Zheng; Zengqiang Yuan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-8
Journal Detail:
Title:  The Biochemical journal     Volume:  -     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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