Journal ArticleDOI
Mutations in the DJ-1 Gene Associated with Autosomal Recessive Early-Onset Parkinsonism
Vincenzo Bonifati,Vincenzo Bonifati,Patrizia Rizzu,Marijke J. van Baren,Onno Schaap,Guido J. Breedveld,Elmar Krieger,Marieke C. J. Dekker,Ferdinando Squitieri,Pablo Ibanez,Marijke Joosse,Jeroen W.F. van Dongen,Nicola Vanacore,Nicola Vanacore,John C. van Swieten,Alexis Brice,Giuseppe Meco,Cornelia M. van Duijn,Ben A. Oostra,Peter Heutink +19 more
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TLDR
It is shown that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism, and these findings indicate that loss ofDJ-1 function leads to neurodegeneration.Abstract:
The DJ-1 gene encodes a ubiquitous, highly conserved protein. Here, we show that DJ-1 mutations are associated with PARK7, a monogenic form of human parkinsonism. The function of the DJ-1 protein remains unknown, but evidence suggests its involvement in the oxidative stress response. Our findings indicate that loss of DJ-1 function leads to neurodegeneration. Elucidating the physiological role of DJ-1 protein may promote understanding of the mechanisms of brain neuronal maintenance and pathogenesis of Parkinson's disease.read more
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DJ-1 Up-regulates Glutathione Synthesis during Oxidative Stress and Inhibits A53T α-Synuclein Toxicity
Wenbo Zhou,Curt R. Freed +1 more
TL;DR: It is concluded that DJ-1 has multiple specific mechanisms for protecting dopamine neurons from cell death through up-regulation of glutathione synthesis and from the toxic consequences of mutant humanα-synuclein through increased expression of heat shock protein 70.
Journal ArticleDOI
Parkin, PINK1, and DJ-1 form a ubiquitin E3 ligase complex promoting unfolded protein degradation
Hui Xiong,Danling Wang,Linan Chen,Yeun Su Choo,Hong Ma,Chengyuan Tang,Kun Xia,Wei Jiang,Ze'ev Ronai,Xiaoxi Zhuang,Zhuohua Zhang +10 more
TL;DR: It is shown that Parkin, PINK1, and DJ-1 formed a complex to promote ubiquitination and degradation of Parkin substrates, including Parkin itself and Synphilin-1 in neuroblastoma cells and human brain lysates and suggests that their PD-pathogenic mutations impair E3 ligase activity of the complex, which may constitute a mechanism underlying PD pathogenesis.
Journal ArticleDOI
Drosophila DJ-1 mutants are selectively sensitive to environmental toxins associated with Parkinson's disease.
Marc C. Meulener,Alexander J. Whitworth,Cecilia E. Armstrong-Gold,Patrizia Rizzu,Peter Heutink,Paul D. Wes,Leo J. Pallanck,Nancy M. Bonini,Nancy M. Bonini +8 more
TL;DR: It is demonstrated that fly DJ-1 activity is selectively involved in protection from environmental oxidative insult in vivo and that theDJ-1beta protein is biochemically responsive to oxidative stress.
Journal ArticleDOI
Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6
James A. Olzmann,Lian Li,Maksim V. Chudaev,Jue Chen,Francisco A. Perez,Richard D. Palmiter,Lih-Shen Chin +6 more
TL;DR: Findings reveal a signaling role for K63-linked polyubiquitination in dynein-mediated transport, identify parkin as a key regulator in the recruitment of misfolded DJ-1 to aggresomes, and have important implications regarding the biogenesis of Lewy bodies.
Journal ArticleDOI
Cysteine-106 of DJ-1 is the most sensitive cysteine residue to hydrogen peroxide-mediated oxidation in vivo in human umbilical vein endothelial cells
TL;DR: The structural characterization of an acidic isoform of DJ-1 using a proteomic approach with nanospray interface liquid chromatography-electrospray ionization/linear ion trap mass spectrometer suggests thatDJ-1 function is regulated, in terms of the intracellular redox state, by oxidation of Cys-106.
References
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Daisuke Nagakubo,Takahiro Taira,Hirotake Kitaura,Masako Ikeda,Katsuyuki Tamai,Sanae M.M. Iguchi-Ariga,Hiroyoshi Ariga +6 more
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