Journal
JOURNAL OF PROTEOME RESEARCH
Volume 10, Issue 10, Pages 4388-4404Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr200225c
Keywords
DJ-1; Hsp90; interactome; iTRAQ mass spectrometry; tcTPC
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Funding
- Canadian Institutes of Health Research
- Canada Foundation for Innovation
- Alexander von Humboldt Foundation
- MRC [MC_G1000734] Funding Source: UKRI
- Medical Research Council [MC_G1000734] Funding Source: researchfish
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DJ-1 is a small but relatively abundant protein of unknown function that may undergo stress-dependent cellular translocation and has been implicated in both neurodegenerative diseases and cancer. As such, DJ-1 may be an excellent study object to elucidate the relative influence of the cellular context on its interactome and for exploring whether acute exposure to oxidative stressors alters its molecular environment. Using quantitative mass spectrometry, we conducted comparative DJ-1 interactome analyses from in vivo cross-linked brains or livers and from hydrogen peroxide-treated or nave embryonic stem cells. The analysis identified a subset of glycolytic enzymes, heat shock proteins 70 and 90, and peroxiredoxins as interactors of DJ-1. Consistent with a role of DJ-1 in Hsp90 chaperone biology, we document destabilization of Hsp90 clients in DJ-1 knockout cells. We further demonstrate the existence of a C106 sulfinic acid modification within DJ-1 and thereby establish that this previously inferred modification also exists in vivo. Our data suggest that caution has to be exerted in interpreting interactome data obtained from a single biological source material and identify a role of DJ-1 as an oxidative stress sensor and partner of a molecular machinery notorious for its involvement in cell fate decisions.
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