The role of cysteine oxidation in DJ-1 function and dysfunction

• Published in: Antioxidants & redox signaling Vol. 15; no. 1; p. 111
• Main Author: Wilson, Mark A
• Format: Journal Article
• Language: English
• Published: United States 01.07.2011
• Subjects: Animals; Cysteine - metabolism; Humans; Intracellular Signaling Peptides and Proteins - chemistry; Intracellular Signaling Peptides and Proteins - metabolism; Models, Biological; Oncogene Proteins - chemistry; Oncogene Proteins - metabolism; Oxidation-Reduction; Peroxiredoxins; Protein Deglycase DJ-1
• ISSN: 1557-7716
• DOI: 10.1089/ars.2010.3481

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.