The role of cysteine oxidation in DJ-1 function and dysfunction.
DJ-1 is a member of the large and functionally diverse DJ-1/PfpI superfamily and has homologs in nearly all organisms. Because of its connection to parkinsonism and cancer, human DJ-1 has been intensely studied for over a decade. The current view is that DJ-1 is a multifunctional oxidative stress response protein that defends cells against reactive oxygen species and mitochondrial damage, although the details of its biochemical function remain unclear. A conserved cysteine residue in DJ-1 (Cys106) is both functionally essential and subject to oxidation to the cysteine-sulfinate and cysteine-sulfonate. Consequently, the oxidative modification of Cys106 has been proposed to allow DJ-1 to act as a sensor of cellular redox homeostasis and to participate in cytoprotective signaling pathways in the cell. This review explores the current evidence for the role of cysteine oxidation in DJ-1 function, with emphasis on emerging models for how oxidative modification may regulate DJ-1's protective function and also contribute to dysfunction and disease.
Wilson
Mark A
MA
Department of Biochemistry, Redox Biology Center, The University of Nebraska-Lincoln, 68588-0664, USA. mwilson13@unl.edu
D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D015513:Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D054464:Peroxiredoxins; C105131:PARK7 protein, human; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D003545:Cysteine
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